The ongoing pursuit of neuroprotective therapies in Parkinson disease (original) (raw)
Duncan, G. W. et al. Health-related quality of life in early Parkinson's disease: the impact of nonmotor symptoms. Mov. Disord.29, 195–202 (2014). ArticlePubMed Google Scholar
Lawson, R. A. et al. Severity of mild cognitive impairment in early Parkinson's disease contributes to poorer quality of life. Parkinsonism Relat. Disord.20, 1071–1075 (2014). ArticlePubMedPubMed Central Google Scholar
Hirsch, E. C., Jenner, P. & Przedborski, S. Pathogenesis of Parkinson's disease. Mov. Disord.28, 24–30 (2013). ArticleCASPubMed Google Scholar
Schapira, A. H. V. & Tolosa, E. Molecular and clinical prodrome of Parkinson disease: implications for treatment. Nat. Rev. Neurol.6, 309–317 (2010). ArticleCASPubMed Google Scholar
Foltynie, T. & Kahan, J. Parkinson's disease: an update on pathogenesis and treatment. J. Neurol.260, 1433–1440 (2013). ArticleCASPubMed Google Scholar
Schapira, A. H. V., Olanow, C. W., Greenamyre, J. T. & Bezard, E. Slowing of neurodegeneration in Parkinson's disease and Huntington's disease: future therapeutic perspectives. Lancet384, 545–555 (2014). ArticleCASPubMed Google Scholar
Olanow, C. W. & Kordower, J. H. Modeling Parkinson's disease. Ann. Neurol.66, 432–436 (2009). ArticleCASPubMed Google Scholar
Blandini, F. & Armentero, M.-T. Animal models of Parkinson's disease. FEBS J.279, 1156–1166 (2012). ArticleCASPubMed Google Scholar
Bezard, E., Yue, Z., Kirik, D. & Spillantini, M. G. Animal models of Parkinson's disease: limits and relevance to neuroprotection studies. Mov. Disord.28, 61–70 (2013). ArticleCASPubMed Google Scholar
Pifl, C., Schingnitz, G. & Hornykiewicz, O. Effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine on the regional distribution of brain monoamines in the rhesus monkey. Neuroscience44, 591–605 (1991). ArticleCASPubMed Google Scholar
Mounayar, S. et al. A new model to study compensatory mechanisms in MPTP-treated monkeys exhibiting recovery. Brain130, 2898–2914 (2007). ArticlePubMed Google Scholar
Iravani, M. M. et al. A modified MPTP treatment regime produces reproducible partial nigrostriatal lesions in common marmosets. Eur. J. Neurosci.21, 841–854 (2005). ArticlePubMed Google Scholar
Duty, S. & Jenner, P. Animal models of Parkinson's disease: a source of novel treatments and clues to the cause of the disease. Br. J. Pharmacol.164, 1357–1391 (2011). ArticleCASPubMedPubMed Central Google Scholar
Ekstrand, M. I. & Galter, D. The MitoPark Mouse—an animal model of Parkinson's disease with impaired respiratory chain function in dopamine neurons. Parkinsonism Relat. Disord.15 (Suppl. 3), S185–S188 (2009). ArticlePubMed Google Scholar
Volpicelli-Daley, L. A. et al. Exogenous α-synuclein fibrils induce Lewy body pathology leading to synaptic dysfunction and neuron death. Neuron72, 57–71 (2011). ArticleCASPubMedPubMed Central Google Scholar
Luk, K. C. & Lee, V. M. Modeling Lewy pathology propagation in Parkinson's disease. Parkinsonism Relat. Disord.20 (Suppl. 1), S85–S87 (2014). ArticlePubMedPubMed Central Google Scholar
Fahn, S. et al. Levodopa and the progression of Parkinson's disease. N. Engl. J. Med.351, 2498–2508 (2004). ArticleCASPubMed Google Scholar
Lang, A. E., Melamed, E., Poewe, W. & Rascol, O. Trial designs used to study neuroprotective therapy in Parkinson's disease. Mov. Disord.28, 86–95 (2013). ArticleCASPubMed Google Scholar
D'Agostino, R. B. Sr. The delayed-start study design. N. Engl. J. Med.361, 1304–1306 (2009). ArticleCASPubMed Google Scholar
Elm, J. J. Design innovations and baseline findings in a long-term Parkinson's trial: the National Institute of Neurological Disorders and stroke exploratory trials in Parkinson's Disease Long-Term Study-1. Mov. Disord.27, 1513–1521 (2012). ArticleCASPubMed Google Scholar
Fearnley, J. M. & Lees, A. J. Ageing and Parkinson's disease: substantia nigra regional selectivity. Brain114, 2283–2301 (1991). ArticlePubMed Google Scholar
Kordower, J. H. et al. Disease duration and the integrity of the nigrostriatal system in Parkinson's disease. Brain136, 2419–2431 (2013). ArticlePubMedPubMed Central Google Scholar
Schwingenschuh, P. et al. Distinguishing SWEDDs patients with asymmetric resting tremor from Parkinson's disease: a clinical and electrophysiological study. Mov. Disord.25, 560–569 (2010). ArticlePubMedPubMed Central Google Scholar
Foltynie, T., Brayne, C. & Barker, R. A. The heterogeneity of idiopathic Parkinson's disease. J. Neurol.249, 138–145 (2002). ArticlePubMed Google Scholar
Dragalin, V. An introduction to adaptive designs and adaptation in CNS trials. Eur. Neuropsychopharmacol.21, 153–158 (2011). ArticleCASPubMed Google Scholar
Kang, J.-H. et al. Association of cerebrospinal fluid β-amyloid 1–42, T-tau, P-tau181, and α-synuclein levels with clinical features of drug-naive patients with early Parkinson disease. JAMA Neurol.70, 1277–1287 (2013). PubMedPubMed Central Google Scholar
Agarwal, P. A. & Stoessl, A. J. Biomarkers for trials of neuroprotection in Parkinson's disease. Mov. Disord.28, 71–85 (2013). ArticleCASPubMed Google Scholar
Olanow, C. W. et al. TCH346 as a neuroprotective drug in Parkinson's disease: a double-blind, randomised, controlled trial. Lancet Neurol.5, 1013–1020 (2006). ArticleCASPubMed Google Scholar
Ward, C. D. Does selegiline delay progression of Parkinson's disease? A critical re-evaluation of the DATATOP study. J. Neurol. Neurosurg. Psychiatry57, 217–220 (1994). ArticleCASPubMedPubMed Central Google Scholar
Sherer, T. B., Chowdhury, S., Peabody, K. & Brooks, D. W. Overcoming obstacles in Parkinson's disease. Mov. Disord.27, 1606–1611 (2012). ArticlePubMed Google Scholar
Tardiff, D. F. et al. Yeast reveal a “druggable” Rsp5/Nedd4 network that ameliorates α-synuclein toxicity in neurons. Science342, 979–983 (2013). ArticleCASPubMedPubMed Central Google Scholar
Chung, C. Y. et al. Identification and rescue of α-synuclein toxicity in Parkinson patient-derived neurons. Science342, 983–987 (2013). ArticleCASPubMedPubMed Central Google Scholar
Mortiboys, H., Aasly, J. & Bandmann, O. Ursocholanic acid rescues mitochondrial function in common forms of familial Parkinson's disease. Brain136, 3038–3050 (2013). ArticlePubMed Google Scholar
Chan, C. S., Gertler, T. S. & Surmeier, D. J. A molecular basis for the increased vulnerability of substantia nigra dopamine neurons in aging and Parkinson's disease. Mov. Disord.25 (Suppl. 1), S63–S70 (2010). ArticlePubMed Google Scholar
Hurley, M. J., Brandon, B., Gentleman, S. M. & Dexter, D. T. Parkinson's disease is associated with altered expression of CaV1 channels and calcium-binding proteins. Brain136, 2077–2097 (2013). ArticlePubMed Google Scholar
Becker, C., Jick, S. S. & Meier, C. R. Use of antihypertensives and the risk of Parkinson disease. Neurology70, 1438–1444 (2008). ArticleCASPubMed Google Scholar
Ritz, B. et al. L-type calcium channel blockers and Parkinson disease in Denmark. Ann. Neurol.67, 600–606 (2010). CASPubMedPubMed Central Google Scholar
Pasternak, B. et al. Use of calcium channel blockers and Parkinson's disease. Am. J. Epidemiol.175, 627–635 (2012). ArticlePubMed Google Scholar
Marras, C. et al. Dihydropyridine calcium channel blockers and the progression of parkinsonism. Ann. Neurol.71, 362–369 (2012). ArticleCASPubMed Google Scholar
Ilijic, E., Guzman, J. N. & Surmeier, D. J. The L-type channel antagonist isradipine is neuroprotective in a mouse model of Parkinson's disease. Neurobiol. Dis.43, 364–371 (2011). ArticleCASPubMedPubMed Central Google Scholar
Chan, C. S. et al. “Rejuvenation” protects neurons in mouse models of Parkinson's disease. Nature447, 1081–1086 (2007). ArticleCASPubMed Google Scholar
Phase II safety, tolerability, and dose selection study of isradipine as a potential disease-modifying intervention in early Parkinson's disease (STEADY-PD). Mov. Disord.28, 1823–1831 (2013).
Kang, S. et al. CaV1.3-selective L-type calcium channel antagonists as potential new therapeutics for Parkinson's disease. Nat. Commun.3, 1146 (2012). ArticlePubMedCAS Google Scholar
Okada, M. et al. Exocytosis mechanism as a new targeting site for mechanisms of action of antiepileptic drugs. Life Sci.72, 465–473 (2002). ArticleCASPubMed Google Scholar
Mochio, S. et al. Actigraphic study of tremor before and after treatment with zonisamide in patients with Parkinson's disease. Parkinsonism Relat. Disord.18, 906–908 (2012). ArticlePubMed Google Scholar
Asanuma, M. et al. Neuroprotective effects of zonisamide target astrocyte. Ann. Neurol.67, 239–249 (2010). ArticleCASPubMed Google Scholar
Alam, Z. I. et al. Oxidative DNA damage in the parkinsonian brain: an apparent selective increase in 8-hydroxyguanine levels in substantia nigra. J. Neurochem.69, 1196–1203 (1997). ArticleCASPubMed Google Scholar
Pålhagen, S. et al. Selegiline slows the progression of the symptoms of Parkinson disease. Neurology66, 1200–1206 (2006). ArticlePubMed Google Scholar
Olanow, C. W. et al. A double-blind, delayed-start trial of rasagiline in Parkinson's disease. N. Engl. J. Med.361, 1268–1278 (2009). ArticleCASPubMed Google Scholar
Weisskopf, M. G., O'Reilly, E., Chen, H., Schwarzschild, M. A. & Ascherio, A. Plasma urate and risk of Parkinson's disease. Am. J. Epidemiol.166, 561–567 (2007). ArticleCASPubMed Google Scholar
Alonso, A., Rodríguez, L. A. G., Logroscino, G. & Hernán, M. A. Gout and risk of Parkinson disease: a prospective study. Neurology69, 1696–1700 (2007). ArticlePubMed Google Scholar
Shen, C., Guo, Y., Luo, W., Lin, C. & Ding, M. Serum urate and the risk of Parkinson's disease: results from a meta-analysis. Can. J. Neurol. Sci.40, 73–79 (2013). ArticlePubMed Google Scholar
Schwarzschild, M. A. et al. Serum urate as a predictor of clinical and radiographic progression in Parkinson disease. Arch. Neurol.65, 716–723 (2008). ArticlePubMedPubMed Central Google Scholar
Ascherio, A. et al. Urate as a predictor of the rate of clinical decline in Parkinson disease. Arch. Neurol.66, 1460–1468 (2009). ArticlePubMedPubMed Central Google Scholar
Andreadou, E. et al. Serum uric acid levels in patients with Parkinson's disease: their relationship to treatment and disease duration. Clin. Neurol. Neurosurg.111, 724–728 (2009). ArticlePubMed Google Scholar
Yamamoto, T. et al. Effect of inosine on the plasma concentration of uridine and purine bases. Metabolism51, 438–442 (2002). ArticleCASPubMed Google Scholar
Schwarzschild, M. A. et al. Inosine to increase serum and cerebrospinal fluid urate in Parkinson disease: a randomized clinical trial. JAMA Neurol.71, 141–150 (2014). ArticlePubMed Google Scholar
Grayson, P. C., Kim, S. Y., LaValley, M. & Choi, H. K. Hyperuricemia and incident hypertension: a systematic review and meta-analysis. Arthritis Care Res. (Hoboken)63, 102–110 (2011). ArticleCAS Google Scholar
Takanashi, M. et al. Iron accumulation in the substantia nigra of autosomal recessive juvenile parkinsonism (ARJP). Parkinsonism Relat. Disord.7, 311–314 (2001). ArticleCASPubMed Google Scholar
Sian-Hülsmann, J., Mandel, S., Youdim, M. B. & Riederer, P. The relevance of iron in the pathogenesis of Parkinson's disease. J. Neurochem.118, 939–957 (2011). ArticlePubMedCAS Google Scholar
Crichton, R. & Ward, R. in Metal-Based Neurodegeneration: From Molecular Mechanisms to Therapeutic Strategies 2nd edn Vol. 1 Ch. 6 148–153 (John Wiley & Sons, 2014). Google Scholar
Jamuar, S. S. & Lai, A. H. Safety and efficacy of iron chelation therapy with deferiprone in patients with transfusion-dependent thalassemia. Ther. Adv. Hematol.3, 299–307 (2012). ArticleCASPubMedPubMed Central Google Scholar
Molina-Holgado, F., Gaeta, A., Francis, P. T., Williams, R. J. & Hider, R. C. Neuroprotective actions of deferiprone in cultured cortical neurones and SHSY-5Y cells. J. Neurochem.105, 2466–2476 (2008). ArticleCASPubMed Google Scholar
Dexter, D. T. et al. Clinically available iron chelators induce neuroprotection in the 6-OHDA model of Parkinson's disease after peripheral administration. J. Neural Transm.118, 223–231 (2011). ArticleCASPubMed Google Scholar
Devos, D. et al. Targeting chelatable iron as a therapeutic modality in Parkinson's disease. Antioxid. Redox Signal.21, 195–210 (2014). ArticleCASPubMedPubMed Central Google Scholar
Hauser, R. A., Lyons, K. E., McClain, T., Carter, S. & Perlmutter, D. Randomized, double-blind, pilot evaluation of intravenous glutathione in Parkinson's disease. Mov. Disord.24, 979–983 (2009). ArticlePubMed Google Scholar
Chinta, S. J. & Andersen, J. K. Reversible inhibition of mitochondrial complex I activity following chronic dopaminergic glutathione depletion in vitro: implications for Parkinson's disease. Free Radic. Biol. Med.41, 1442–1448 (2006). ArticleCASPubMed Google Scholar
Sian, J. et al. Alterations in glutathione levels in Parkinson's disease and other neurodegenerative disorders affecting basal ganglia. Ann. Neurol.36, 348–355 (1994). ArticleCASPubMed Google Scholar
Riederer, P. et al. Transition metals, ferritin, glutathione, and ascorbic acid in parkinsonian brains. J. Neurochem.52, 515–520 (1989). ArticleCASPubMed Google Scholar
Dexter, D. T. et al. Indices of oxidative stress and mitochondrial function in individuals with incidental Lewy body disease. Ann. Neurol.35, 38–44 (1994). ArticleCASPubMed Google Scholar
Hauser, R. A., Lyons, K. E., McClain, T., Carter, S. & Perlmutter, D. Randomized, double-blind, pilot evaluation of intravenous glutathione in Parkinson's disease. Mov. Disord.24, 979–983 (2009). ArticlePubMed Google Scholar
Clark, J. et al. Oral _N_-acetyl-cysteine attenuates loss of dopaminergic terminals in α-synuclein overexpressing mice. PLoS ONE5, e12333 (2010). ArticlePubMedPubMed CentralCAS Google Scholar
Katz, M., Swanson, R. A., Glass, G. A. Cerebrospinal fluid concentrations of _N_-acetylcysteine after oral administration: phase I trial in Parkinson's disease [abstract 664]. Mov. Disord.29 (Suppl. 1), S247 (2014). Google Scholar
Adair, J. C., Knoefel, J. E. & Morgan, N. Controlled trial of _N_-acetylcysteine for patients with probable Alzheimer's disease. Neurology57, 1515–1517 (2001). ArticleCASPubMed Google Scholar
Schapira, A. H. Mitochondria in the aetiology and pathogenesis of Parkinson's disease. Lancet Neurol.7, 97–109 (2008). ArticleCASPubMed Google Scholar
Carta, A. R. & Pisanu, A. Modulating microglia activity with PPAR-γ agonists: a promising therapy for Parkinson's disease? Neurotox. Res.23, 112–123 (2013). ArticleCASPubMed Google Scholar
Khan, M. M. et al. Resveratrol attenuates 6-hydroxydopamine-induced oxidative damage and dopamine depletion in rat model of Parkinson's disease. Brain Res.1328, 139–151 (2010). ArticleCASPubMed Google Scholar
Lofrumento, D. D. et al. Neuroprotective effects of resveratrol in an MPTP mouse model of Parkinson's-like disease: possible role of SOCS-1 in reducing pro-inflammatory responses. Innate Immun.20, 249–260 (2014). ArticlePubMedCAS Google Scholar
Rees, K. et al. Non-steroidal anti-inflammatory drugs as disease-modifying agents for Parkinson's disease: evidence from observational studies. Cochrane Database of Systematic Reviews, Issue 1. Art. No.: CD008454. http://dx.doi.org/10.1002/14651858.CD008454.pub2.
Bartels, A. L. et al. [11C]-PK11195 PET: quantification of neuroinflammation and a monitor of anti-inflammatory treatment in Parkinson's disease? Parkinsonism Relat. Disord.16, 57–59 (2010). ArticleCASPubMed Google Scholar
Imamura, K. et al. Distribution of major histocompatibility complex class II-positive microglia and cytokine profile of Parkinson's disease brains. Acta Neuropathol.106, 518–526 (2003). ArticleCASPubMed Google Scholar
International Parkinson's Disease Genomics Consortium (IPDGC) & Wellcome Trust Case Control Consortium 2 (WTCCC2). A two-stage meta-analysis identifies several new loci for Parkinson's disease. PLoS Genet.7, e1002142 (2011).
Diani, A. R., Sawada, G., Wyse, B., Murray, F. T. & Khan, M. Pioglitazone preserves pancreatic islet structure and insulin secretory function in three murine models of type 2 diabetes. Am. J. Physiol. Endocrinol. Metab.286, E116–E122 (2004). ArticleCASPubMed Google Scholar
Heneka, M. T. et al. Acute treatment with the PPARγ agonist pioglitazone and ibuprofen reduces glial inflammation and Aβ1–42 levels in APPV717I transgenic mice. Brain128, 1442–1453 (2005). ArticlePubMed Google Scholar
Okada, K., Yamashita, U. & Tsuji, S. Ameliorative effect of pioglitazone on seizure responses in genetically epilepsy-susceptible EL mice. Brain Res.1102, 175–178 (2006). ArticleCASPubMed Google Scholar
Nakamura, T. et al. Pioglitazone exerts protective effects against stroke in stroke-prone spontaneously hypertensive rats, independently of blood pressure. Stroke38, 3016–3022 (2007). ArticleCASPubMed Google Scholar
Schütz, B. et al. The oral antidiabetic pioglitazone protects from neurodegeneration and amyotrophic lateral sclerosis-like symptoms in superoxide dismutase-G93A transgenic mice. J. Neurosci.25, 7805–7812 (2005). ArticlePubMedPubMed CentralCAS Google Scholar
Dehmer, T., Heneka, M. T., Sastre, M., Dichgans, J. & Schulz, J. B. Protection by pioglitazone in the MPTP model of Parkinson's disease correlates with IκB alpha induction and block of NFκB and iNOS activation. J. Neurochem.88, 494–501 (2004). ArticleCASPubMed Google Scholar
Breidert, T. et al. Protective action of the peroxisome proliferator-activated receptor-γ agonist pioglitazone in a mouse model of Parkinson's disease. J. Neurochem.82, 615–624 (2002). ArticleCASPubMed Google Scholar
Swanson, C. R. et al. The PPAR-γ agonist pioglitazone modulates inflammation and induces neuroprotection in parkinsonian monkeys. J. Neuroinflammation8, 91 (2011). ArticleCASPubMedPubMed Central Google Scholar
Suzuki, S. et al. Effects of pioglitazone, a peroxisome proliferator-activated receptor gamma agonist, on the urine and urothelium of the rat. Toxicol. Sci.113, 349–357 (2010). ArticleCASPubMed Google Scholar
Azoulay, L. et al. The use of pioglitazone and the risk of bladder cancer in people with type 2 diabetes: nested case-control study. BMJ344, e3645 (2012). ArticlePubMedPubMed Central Google Scholar
Ferwana, M. et al. Pioglitazone and risk of bladder cancer: a meta-analysis of controlled studies. Diabet. Med.30, 1026–1032 (2013). ArticleCASPubMed Google Scholar
Consoli, A. & Formoso, G. Do thiazolidinediones still have a role in treatment of type 2 diabetes mellitus? Diabetes Obes. Metab.15, 967–977 (2013). ArticleCASPubMed Google Scholar
Colca, J. R. et al. Identification of a mitochondrial target of thiazolidinedione insulin sensitizers (mTOT)—relationship to newly identified mitochondrial pyruvate carrier proteins. PLoS ONE8, e61551 (2013). ArticleCASPubMedPubMed Central Google Scholar
Colca, J. R. et al. Identification of a novel mitochondrial protein (“mitoNEET”) cross-linked specifically by a thiazolidinedione photoprobe. Am. J. Physiol. Endocrinol. Metab.286, E252–E260 (2004). ArticleCASPubMed Google Scholar
Colca, J. R. et al. Clinical proof-of-concept study with MSDC-0160, a prototype mTOT-modulating insulin sensitizer. Clin. Pharmacol. Ther.93, 352–359 (2013). ArticleCASPubMedPubMed Central Google Scholar
Appel, S. H. Inflammation in Parkinson's disease: cause or consequence? Mov. Disord.27, 1075–1077 (2012). ArticleCASPubMed Google Scholar
Choi, D.-K. et al. Ablation of the inflammatory enzyme myeloperoxidase mitigates features of Parkinson's disease in mice. J. Neurosci.25, 6594–6600 (2005). ArticleCASPubMedPubMed Central Google Scholar
Posener, J. A., et al. Safety, tolerability, and pharmacodynamics of AZD3241, a myeloperoxidase inhibitor, in Parkinson's disease [abstract 698]. Mov. Disord.29 (Suppl. 1), S259–S260 (2014). Google Scholar
Selley, M. L. Simvastatin prevents 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced striatal dopamine depletion and protein tyrosine nitration in mice. Brain Res.1037, 1–6 (2005). ArticleCASPubMed Google Scholar
Wang, Q., Wang, P. H., McLachlan, C. & Wong, P. T. Simvastatin reverses the downregulation of dopamine D1 and D2 receptor expression in the prefrontal cortex of 6-hydroxydopamine-induced Parkinsonian rats. Brain Res.1045, 229–233 (2005). ArticleCASPubMed Google Scholar
Hernández-Romero, M. C. et al. Simvastatin prevents the inflammatory process and the dopaminergic degeneration induced by the intranigral injection of lipopolysaccharide. J. Neurochem.105, 445–459 (2008). ArticlePubMedCAS Google Scholar
Santiago, M., Hernández-Romero, M. C., Machado, A. & Cano, J. Zocor Forte® (simvastatin) has a neuroprotective effect against LPS striatal dopaminergic terminals injury, whereas against MPP+ does not. Eur. J. Pharmacol.609, 58–64 (2009). ArticleCASPubMed Google Scholar
Yan, J., Sun, J., Huang, L., Fu, Q. & Du, G. Simvastatin prevents neuroinflammation by inhibiting _N_-methyl-D-aspartic acid receptor 1 in 6-hydroxydopamine-treated PC12 cells. J. Neurosci. Res.92, 634–640 (2014). ArticleCASPubMed Google Scholar
Bar-On, P. et al. Statins reduce neuronal α-synuclein aggregation in in vitro models of Parkinson's disease. J. Neurochem.105, 1656–1667 (2008). ArticleCASPubMedPubMed Central Google Scholar
Gao, X., Simon, K. C., Schwarzschild, M. A. & Ascherio, A. Prospective study of statin use and risk of Parkinson disease. Arch. Neurol.69, 380–384 (2012). ArticlePubMedPubMed Central Google Scholar
Wahner, A. D., Bronstein, J. M., Bordelon, Y. M. & Ritz, B. Statin use and the risk of Parkinson disease. Neurology70, 1418–1422 (2008). ArticleCASPubMed Google Scholar
Becker, C., Jick, S. S. & Meier, C. R. Use of statins and the risk of Parkinson's disease: a retrospective case-control study in the UK. Drug Saf.31, 399–407 (2008). ArticleCASPubMed Google Scholar
Hippisley-Cox, J. & Coupland, C. Unintended effects of statins in men and women in England and Wales: population based cohort study using the QResearch database. BMJ340, c2197 (2010). ArticlePubMedPubMed Central Google Scholar
Huang, X. et al. Lower low-density lipoprotein cholesterol levels are associated with Parkinson's disease. Mov. Disord.22, 377–381 (2007). ArticlePubMedPubMed Central Google Scholar
Lee, Y.-C. et al. Discontinuation of statin therapy associates with Parkinson disease: a population-based study. Neurology81, 410–416 (2013). ArticleCASPubMed Google Scholar
Martin, F. L., Williamson, S. J., Paleologou, K. E., Allsop, D. & El-Agnaf, O. M. α-Synuclein and the pathogenesis of Parkinson's disease. Protein Pept. Lett.11, 229–237 (2004). ArticleCASPubMed Google Scholar
Li, J.-Y. et al. Lewy bodies in grafted neurons in subjects with Parkinson's disease suggest host-to-graft disease propagation. Nat. Med.14, 501–503 (2008). ArticleCASPubMed Google Scholar
Desplats, P. et al. Inclusion formation and neuronal cell death through neuron-to-neuron transmission of alpha-synuclein. Proc. Natl Acad. Sci. USA106, 13010–13015 (2009). ArticleCASPubMedPubMed Central Google Scholar
Hansen, C. et al. α-Synuclein propagates from mouse brain to grafted dopaminergic neurons and seeds aggregation in cultured human cells. J. Clin. Invest.121, 715–725 (2011). ArticleCASPubMedPubMed Central Google Scholar
Mougenot, A.-L. et al. Prion-like acceleration of a synucleinopathy in a transgenic mouse model. Neurobiol. Aging33, 2225–2228 (2012). ArticleCASPubMed Google Scholar
Tóth, G. et al. Targeting the intrinsically disordered structural ensemble of α-synuclein by small molecules as a potential therapeutic strategy for Parkinson's disease. PLoS ONE9, e87133 (2014). ArticlePubMedPubMed CentralCAS Google Scholar
Masliah, E. et al. Effects of α-synuclein immunization in a mouse model of Parkinson's disease. Neuron46, 857–868 (2005). ArticleCASPubMed Google Scholar
Masliah, E. et al. Passive immunization reduces behavioral and neuropathological deficits in an alpha-synuclein transgenic model of Lewy body disease. PLoS ONE6, e19338 (2011). ArticleCASPubMedPubMed Central Google Scholar
Schneeberger, A, Mandler, M., Mattner, F. & Schmidt, W. Vaccination for Parkinson's disease. Parkinsonism Relat. Disord.18 (Suppl. 1), S11–S13 (2012). ArticlePubMed Google Scholar
Anderson, J. P. et al. Phosphorylation of Ser-129 is the dominant pathological modification of α-synuclein in familial and sporadic Lewy body disease. J. Biol. Chem.281, 29739–29752 (2006). ArticleCASPubMed Google Scholar
Pérez-Revuelta, B. I. et al. Metformin lowers Ser-129 phosphorylated α-synuclein levels via mTOR-dependent protein phosphatase 2A activation. Cell Death Dis.5, e1209 (2014). ArticlePubMedPubMed CentralCAS Google Scholar
Wahlqvist, M. L. et al. Metformin-inclusive sulfonylurea therapy reduces the risk of Parkinson's disease occurring with type 2 diabetes in a Taiwanese population cohort. Parkinsonism Relat. Disord.18, 753–758 (2012). ArticlePubMed Google Scholar
Steele, J. W. et al. Latrepirdine stimulates autophagy and reduces accumulation of α-synuclein in cells and in mouse brain. Mol. Psychiatry18, 882–888 (2013). ArticleCASPubMed Google Scholar
Duran, R. et al. The glucocerobrosidase E326K variant predisposes to Parkinson's disease, but does not cause Gaucher's disease. Mov. Disord.28, 232–236 (2013). ArticleCASPubMed Google Scholar
Neumann, J. et al. Glucocerebrosidase mutations in clinical and pathologically proven Parkinson's disease. Brain132, 1783–1794 (2009). ArticlePubMedPubMed Central Google Scholar
Sardi, S. P. et al. Augmenting CNS glucocerebrosidase activity as a therapeutic strategy for parkinsonism and other Gaucher-related synucleinopathies. Proc. Natl Acad. Sci. USA110, 3537–3542 (2013). ArticleCASPubMedPubMed Central Google Scholar
Zimran, A., Altarescu, G. & Elstein, D. Pilot study using ambroxol as a pharmacological chaperone in type 1 Gaucher disease. Blood Cells Mol. Dis.50, 134–137 (2013). ArticleCASPubMed Google Scholar
Bendikov-Bar, I., Maor, G., Filocamo, M. & Horowitz, M. Ambroxol as a pharmacological chaperone for mutant glucocerebrosidase. Blood Cells Mol. Dis.50, 141–145 (2013). ArticleCASPubMedPubMed Central Google Scholar
Olanow, C. W. & Schapira, A. H. Therapeutic prospects for Parkinson disease. Ann. Neurol.74, 337–347 (2013). ArticleCASPubMed Google Scholar
Richter, F. et al. A GCase chaperone improves motor function in a mouse model of synucleinopathy. Neurotherapeutics11, 840–856 (2014). ArticleCASPubMedPubMed Central Google Scholar
Wu, G., Lu, Z.-H., Kulkarni, N., Amin, R. & Ledeen, R. W. Mice lacking major brain gangliosides develop parkinsonism. Neurochem. Res.36, 1706–1714 (2011). ArticleCASPubMedPubMed Central Google Scholar
Schneider, J. S. et al. Recovery from experimental parkinsonism in primates with GM1 ganglioside treatment. Science256, 843–846 (1992). ArticleCASPubMed Google Scholar
Schneider, J. S., Sendek, S., Daskalakis, C. & Cambi, F. GM1 ganglioside in Parkinson's disease: results of a five year open study. J. Neurol. Sci.292, 45–51 (2010). ArticleCASPubMed Google Scholar
Schneider, J. S. et al. A randomized, controlled, delayed start trial of GM1 ganglioside in treated Parkinson's disease patients. J. Neurol. Sci.324, 140–148 (2013). ArticleCASPubMed Google Scholar
Parkes, D. G., Mace, K. F. & Trautmann, M. E. Discovery and development of exenatide: the first antidiabetic agent to leverage the multiple benefits of the incretin hormone, GLP-1. Expert Opin. Drug Discov.8, 219–244 (2013). ArticleCASPubMed Google Scholar
Perry, T., Haughey, N. J., Mattson, M. P., Egan, J. M. & Greig, N. H. Protection and reversal of excitotoxic neuronal damage by glucagon-like peptide-1 and exendin-4. J. Pharmacol. Exp. Ther.302, 881–888 (2002). ArticleCASPubMed Google Scholar
Perry, T. et al. A novel neurotrophic property of glucagon-like peptide 1: a promoter of nerve growth factor-mediated differentiation in PC12 cells. J. Pharmacol. Exp. Ther.300, 958–966 (2002). ArticleCASPubMed Google Scholar
Harkavyi, A. et al. Glucagon-like peptide 1 receptor stimulation reverses key deficits in distinct rodent models of Parkinson's disease. J. Neuroinflammation5, 19 (2008). ArticlePubMedPubMed CentralCAS Google Scholar
Kim, S., Moon, M. & Park, S. Exendin-4 protects dopaminergic neurons by inhibition of microglial activation and matrix metalloproteinase-3 expression in an animal model of Parkinson's disease. J. Endocrinol.202, 431–439 (2009). ArticleCASPubMed Google Scholar
Bertilsson, G. et al. Peptide hormone exendin-4 stimulates subventricular zone neurogenesis in the adult rodent brain and induces recovery in an animal model of Parkinson's disease. J. Neurosci. Res.86, 326–338 (2008). ArticleCASPubMed Google Scholar
Rampersaud, N. et al. Exendin-4 reverses biochemical and behavioral deficits in a pre-motor rodent model of Parkinson's disease with combined noradrenergic and serotonergic lesions. Neuropeptides46, 183–193 (2012). ArticleCASPubMed Google Scholar
Chen, S., Liu, A., An, F., Yao, W. & Gao, X. Amelioration of neurodegenerative changes in cellular and rat models of diabetes-related Alzheimer's disease by exendin-4. Age (Dordr.)34, 1211–1224 (2012). ArticleCAS Google Scholar
Aviles-Olmos, I. et al. Exenatide and the treatment of patients with Parkinson's disease. J. Clin. Invest.123, 2364–2365 (2013). ArticleCAS Google Scholar
Aviles-Olmos, I. et al. Motor and cognitive advantages persist 12 months after exenatide exposure in Parkinson's disease. J. Parkinsons Dis.4, 337–444 (2014). ArticleCASPubMed Google Scholar
Ryan, G. J., Moniri, N. H. & Smiley, D. D. Clinical effects of once-weekly exenatide for the treatment of type 2 diabetes mellitus. Am. J. Health Syst. Pharm.70, 1123–1131 (2013). ArticleCASPubMed Google Scholar
Chang, R. C., Ho, Y.-S., Wong, S., Gentleman, S. M. & Ng, H.-K. Neuropathology of cigarette smoking. Acta Neuropathol.127, 53–69 (2014). ArticleCASPubMed Google Scholar
Tsuang, D. et al. Association between lifetime cigarette smoking and Lewy body accumulation. Brain Pathol.20, 412–418 (2010). ArticlePubMed Google Scholar
Hong, D.-P., Fink, A. L. & Uversky, V. N. Smoking and Parkinson's disease: does nicotine affect α-synuclein fibrillation? Biochim. Biophys. Acta1794, 282–290 (2009). ArticleCASPubMed Google Scholar
Quik, M., Perez, X. A. & Bordia, T. Nicotine as a potential neuroprotective agent for Parkinson's disease. Mov. Disord.27, 947–957 (2012). ArticleCASPubMedPubMed Central Google Scholar
Shimohama, S. Nicotinic receptor-mediated neuroprotection in neurodegenerative disease models. Biol. Pharm. Bull.32, 332–336 (2009). ArticleCASPubMed Google Scholar
Ward, R. J., Lallemand, F., de Witte, P. & Dexter, D. T. Neurochemical pathways involved in the protective effects of nicotine and ethanol in preventing the development of Parkinson's disease: potential targets for the development of new therapeutic agents. Prog. Neurobiol.85, 135–147 (2008). ArticleCASPubMed Google Scholar
Costa, G., Abin-Carriquiry, J. A. & Dajas, F. Nicotine prevents striatal dopamine loss produced by 6-hydroxydopamine lesion in the substantia nigra. Brain Res.888, 336–342 (2001). ArticleCASPubMed Google Scholar
Ryan, R. E., Ross, S. A., Drago, J. & Loiacono, R. E. Dose-related neuroprotective effects of chronic nicotine in 6-hydroxydopamine treated rats, and loss of neuroprotection in α4 nicotinic receptor subunit knockout mice. Br. J. Pharmacol.132, 1650–1656 (2001). ArticleCASPubMedPubMed Central Google Scholar
Parain, K., Marchand, V., Dumery, B. & Hirsch, E. Nicotine, but not cotinine, partially protects dopaminergic neurons against MPTP-induced degeneration in mice. Brain Res.890, 347–350 (2001). ArticleCASPubMed Google Scholar
Quik, M. et al. Chronic oral nicotine normalizes dopaminergic function and synaptic plasticity in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned primates. J. Neurosci.26, 4681–4689 (2006). ArticleCASPubMedPubMed Central Google Scholar
Brundin, P. et al. Linked clinical trials—the development of new clinical learning studies in Parkinson's disease using screening of multiple prospective new treatments. J. Parkinsons Dis.3, 231–239 (2013). PubMedPubMed Central Google Scholar
Hely, M. A., Reid, W. G., Adena, M. A., Halliday, G. M. & Morris, J. G. The Sydney multicenter study of Parkinson's disease: the inevitability of dementia at 20 years. Mov. Disord.23, 837–844 (2008). ArticlePubMed Google Scholar
Muslimovic, D., Post, B., Speelman, J. D. & Schmand, B. Cognitive profile of patients with newly diagnosed Parkinson disease. Neurology65, 1239–1245 (2005). ArticlePubMed Google Scholar
Rolinski, M., Fox, C., Maidment, I. & McShane, R. Cholinesterase inhibitors for dementia with Lewy bodies, Parkinson's disease dementia and cognitive impairment in Parkinson's disease. Cochrane Database of Systematic Reviews, Issue 3. Art. No.: CD006504. http://dx.doi.org/10.1002/14651858.CD006504.pub2.
Broadstock, M., Ballard, C. & Corbett, A. Latest treatment options for Alzheimer's disease, Parkinson's disease dementia and dementia with Lewy bodies. Expert Opin. Pharmacother.15, 1797–1810 (2014). ArticleCASPubMed Google Scholar
Masliah, E. et al. β-amyloid peptides enhance α-synuclein accumulation and neuronal deficits in a transgenic mouse model linking Alzheimer's disease and Parkinson's disease. Proc. Natl Acad. Sci. USA98, 12245–12250 (2001). ArticleCASPubMedPubMed Central Google Scholar
Jellinger, K. A., Seppi, K., Wenning, G. K. & Poewe, W. Impact of coexistent Alzheimer pathology on the natural history of Parkinson's disease. J. Neural Transm.109, 329–339 (2002). ArticleCASPubMed Google Scholar
Kotzbauer, P. T. et al. Pathologic accumulation of α-synuclein and Aβ in Parkinson disease patients with dementia. Arch. Neurol.69, 1326–1331 (2012). ArticlePubMedPubMed Central Google Scholar
Compta, Y. et al. Lewy- and Alzheimer-type pathologies in Parkinson's disease dementia: which is more important? Brain134, 1493–1505 (2011). ArticlePubMed Google Scholar
Irwin, D. J., Lee, V. M. & Trojanowski, J. Q. Parkinson's disease dementia: convergence of α-synuclein, tau and amyloid-β pathologies. Nat. Rev. Neurosci.14, 626–636 (2013). ArticleCASPubMedPubMed Central Google Scholar
Simón-Sánchez, J. et al. Genome-wide association study reveals genetic risk underlying Parkinson's disease. Nat. Genet.41, 1308–1312 (2009). ArticlePubMedPubMed CentralCAS Google Scholar
Edwards, T. L. et al. Genome-wide association study confirms SNPs in SNCA and the MAPT region as common risk factors for Parkinson disease. Ann. Hum. Genet.74, 97–109 (2010). ArticleCASPubMedPubMed Central Google Scholar
Goris, A. et al. Tau and α-synuclein in susceptibility to, and dementia in, Parkinson's disease. Ann. Neurol.62, 145–153 (2007). ArticleCASPubMed Google Scholar
Tariot, P. N. et al. Chronic divalproex sodium to attenuate agitation and clinical progression of Alzheimer disease. Arch. Gen. Psychiatry68, 853–861 (2011). ArticleCASPubMedPubMed Central Google Scholar
Zhang, X. et al. Long-term treatment with lithium alleviates memory deficits and reduces amyloid-β production in an aged Alzheimer's disease transgenic mouse model. J. Alzheimers. Dis.24, 739–749 (2011). ArticleCASPubMed Google Scholar
Nunes, M. A., Viel, T. A. & Buck, H. S. Microdose lithium treatment stabilized cognitive impairment in patients with Alzheimer's disease. Curr. Alzheimer Res.10, 104–107 (2013). CASPubMed Google Scholar
Zhang, B. et al. The microtubule-stabilizing agent, epothilone D, reduces axonal dysfunction, neurotoxicity, cognitive deficits, and Alzheimer-like pathology in an interventional study with aged tau transgenic mice. J. Neurosci.32, 3601–3611 (2012). ArticleCASPubMedPubMed Central Google Scholar
Wen, Y. et al. Alternative mitochondrial electron transfer as a novel strategy for neuroprotection. J. Biol. Chem.286, 16504–16515 (2011). ArticleCASPubMedPubMed Central Google Scholar
O'Leary, J. C. et al. Phenothiazine-mediated rescue of cognition in tau transgenic mice requires neuroprotection and reduced soluble tau burden. Mol. Neurodegener.5, 45 (2010). ArticlePubMedPubMed CentralCAS Google Scholar
Spires-Jones, T. L. et al. Methylene blue does not reverse existing neurofibrillary tangle pathology in the rTg4510 mouse model of tauopathy. Neurosci. Lett.562, 63–68 (2014). ArticleCASPubMedPubMed Central Google Scholar
Stack, C. et al. Methylene blue upregulates Nrf2/ARE genes and prevents tau-related neurotoxicity. Hum. Mol. Genet.23, 3716–3732 (2014). ArticleCASPubMedPubMed Central Google Scholar
Wischik, C. M., Bentham, P., Wischik, D. J. & Seng, K. M. Tau aggregation inhibitor (TAI) therapy with rember™ arrests disease progression in mild and moderate Alzheimer's disease over 50 weeks [abstract]. Alzheimers Dement.4 (Suppl. 1). T167 (2008). Article Google Scholar
Braak, H., Rüb, U., Jansen Steur, E. N., Del Tredici, K. & de Vos, R. A. Cognitive status correlates with neuropathologic stage in Parkinson disease. Neurology64, 1404–1410 (2005). ArticleCASPubMed Google Scholar
Hurtig, H. I. et al. Alpha-synuclein cortical Lewy bodies correlate with dementia in Parkinson's disease. Neurology54, 1916–1921 (2000). ArticleCASPubMed Google Scholar
Aarsland, D., Andersen, K., Larsen, J. P., Lolk, A. & Kragh-Sørensen, P. Prevalence and characteristics of dementia in Parkinson disease: an 8-year prospective study. Arch. Neurol.60, 387–392 (2003). ArticlePubMed Google Scholar
Selikhova, M. et al. A clinico-pathological study of subtypes in Parkinson's disease. Brain132, 2947–2957 (2009). ArticleCASPubMed Google Scholar
Weinreb, O., Amit, T., Riederer, P., Youdim, M. B. & Mandel, S. A. Neuroprotective profile of the multitarget drug rasagiline in Parkinson's disease. Int. Rev. Neurobiol.100, 127–149 (2011). ArticleCASPubMed Google Scholar
Beal, M. F. et al. A randomized clinical trial of high-dosage coenzyme Q10 in early Parkinson disease: no evidence of benefit. JAMA Neurol.71, 543–552 (2014). ArticlePubMed Google Scholar
Visanji, N. P. et al. PYM50028, a novel, orally active, nonpeptide neurotrophic factor inducer, prevents and reverses neuronal damage induced by MPP+ in mesencephalic neurons and by MPTP in a mouse model of Parkinson's disease. FASEB J.22, 2488–2497 (2008). ArticleCASPubMed Google Scholar
Jin, H., Kanthasamy, A., Ghosh, A. & Anantharam, V. Mitochondria-targeted antioxidants for treatment of Parkinson's disease: preclinical and clinical outcomes. Biochim Biophys Acta1842, 1282–1294 (2013). ArticlePubMedPubMed CentralCAS Google Scholar
Snow, B. J. et al. A double-blind, placebo-controlled study to assess the mitochondria-targeted antioxidant MitoQ as a disease-modifying therapy in Parkinson's disease. Mov. Disord.25, 1670–1674 (2010). ArticlePubMed Google Scholar
Marks, W. J. et al. Gene delivery of AAV2-neurturin for Parkinson's disease: a double-blind, randomised, controlled trial. Lancet Neurol.9, 1164–1172 (2010). ArticleCASPubMed Google Scholar
Fitton, A. & Benfield, P. Isradipine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in cardiovascular disease. Drugs40, 31–74 (1990). ArticleCASPubMed Google Scholar
Chen, X. et al. Disrupted and transgenic urate oxidase alter urate and dopaminergic neurodegeneration. Proc. Natl Acad. Sci. USA110, 300–305 (2013). ArticleCASPubMed Google Scholar
Boddaert, N. et al. Selective iron chelation in Friedreich ataxia: biologic and clinical implications. Blood110, 401–408 (2007). ArticleCASPubMed Google Scholar
Berman, A. E. et al. N-acetylcysteine prevents loss of dopaminergic neurons in the EAAC1−/− mouse. Ann. Neurol.69, 509–520 (2011). ArticleCASPubMed Google Scholar
Pan, J. et al. Blockade of the translocation and activation of c-Jun N-terminal kinase 3 (JNK3) attenuates dopaminergic neuronal damage in mouse model of Parkinson's disease. Neurochem. Int.54, 418–425 (2009). ArticleCASPubMed Google Scholar
Choudhury, M. E. et al. Zonisamide-induced long-lasting recovery of dopaminergic neurons from MPTP-toxicity. Brain Res.1384, 170–178 (2011). ArticleCASPubMed Google Scholar
Choudhury, M. E. et al. Zonisamide up-regulated the mRNAs encoding astrocytic anti-oxidative and neurotrophic factors. Eur. J. Pharmacol.689, 72–80 (2012). ArticleCASPubMed Google Scholar
Yürekli, V. A., Gürler, S., Nazırog˘lu, M., Ug˘uz, A. C. & Koyuncuog˘lu, H. R. Zonisamide attenuates MPP(+)-induced oxidative toxicity through modulation of Ca2+ signaling and caspase-3 activity in neuronal PC12 cells. Cell. Mol. Neurobiol.33, 205–212 (2013). ArticlePubMedCAS Google Scholar
Murata, M., Hasegawa, K. & Kanazawa, I. Zonisamide improves motor function in Parkinson disease: a randomized, double-blind study. Neurology68, 45–50 (2007). ArticleCASPubMed Google Scholar
Ulusoy, G. K. et al. Effects of pioglitazone and retinoic acid in a rotenone model of Parkinson's disease. Brain Res. Bull.85, 380–384 (2011). ArticleCASPubMed Google Scholar
Haddadi, R., Mohajjel Nayebi, A. & Brooshghalan, S. E. Pre-treatment with silymarin reduces brain myeloperoxidase activity and inflammatory cytokines in 6-OHDA hemi-parkinsonian rats. Neurosci. Lett.555, 106–111 (2013). ArticleCASPubMed Google Scholar
Foltynie, T. & Aviles-Olmos, I. Exenatide as a potential treatment for patients with Parkinson's disease: first steps into the clinic. Alzheimers Dement.10 (Suppl. 1), S38–S46 (2014). ArticlePubMed Google Scholar
Schneider, A. et al. The hematopoietic factor G-CSF is a neuronal ligand that counteracts programmed cell death and drives neurogenesis. J. Clin. Invest.115, 2083–2098 (2005). ArticleCASPubMedPubMed Central Google Scholar
Watson, F. L. et al. Neurotrophins use the Erk5 pathway to mediate a retrograde survival response. Nat. Neurosci.4, 981–988 (2001). ArticleCASPubMed Google Scholar
Jung, K.-H. et al. Granulocyte colony-stimulating factor stimulates neurogenesis via vascular endothelial growth factor with STAT activation. Brain Res.1073–1074, 190–201 (2006). ArticlePubMedCAS Google Scholar
Hartung, T. Anti-inflammatory effects of granulocyte colony-stimulating factor. Curr. Opin. Hematol.5, 221–225 (1998). ArticleCASPubMed Google Scholar
Meuer, K. et al. Granulocyte-colony stimulating factor is neuroprotective in a model of Parkinson's disease. J. Neurochem.97, 675–686 (2006). ArticleCASPubMed Google Scholar
Lee, S.-T. et al. Granulocyte-colony stimulating factor attenuates striatal degeneration with activating survival pathways in 3-nitropropionic acid model of Huntington's disease. Brain Res.1194, 130–137 (2008). ArticleCASPubMed Google Scholar
Xue, Y.-Q., Zhao, L.-R., Guo, W.-P. & Duan, W.-M. Intrastriatal administration of erythropoietin protects dopaminergic neurons and improves neurobehavioral outcome in a rat model of Parkinson's disease. Neuroscience146, 1245–1258 (2007). ArticleCASPubMed Google Scholar
Pedroso, I. et al. Use of Cuban recombinant human erythropoietin in Parkinson's disease treatment. MEDICC Rev.14, 11–17 (2012). PubMed Google Scholar
Jang, W. et al. Safety and efficacy of recombinant human erythropoietin treatment of non-motor symptoms in Parkinson's disease. J. Neurol. Sci.337, 47–54 (2014). ArticleCASPubMed Google Scholar