Innate immune activation in neurodegenerative disease (original) (raw)
Kierdorf, K. et al. Microglia emerge from erythromyeloid precursors via Pu.1- and Irf8-dependent pathways. Nature Neurosci.16, 273–280 (2013). ArticleCASPubMed Google Scholar
Ginhoux, F. et al. Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science330, 841–845 (2010). This paper shows that microglial cell populations originate from the yolk sac and not from the bone marrow, as was previously believed. ArticleCASPubMedPubMed Central Google Scholar
Alliot, F., Godin, I. & Pessac, B. Microglia derive from progenitors, originating from the yolk sac, and which proliferate in the brain. Brain Res. Dev. Brain Res.117, 145–152 (1999). ArticleCASPubMed Google Scholar
Lawson, L. J., Perry, V. H., Dri, P. & Gordon, S. Heterogeneity in the distribution and morphology of microglia in the normal adult mouse brain. Neuroscience39, 151–170 (1990). ArticleCASPubMed Google Scholar
Parkhurst, C. N. et al. Microglia promote learning-dependent synapse formation through brain-derived neurotrophic factor. Cell155, 1596–1609 (2013). This paper shows that microglia have an important role in learning and memory by generating neurotrophic factors, such as BDNF. ArticleCASPubMedPubMed Central Google Scholar
Wake, H., Moorhouse, A. J., Jinno, S., Kohsaka, S. & Nabekura, J. Resting microglia directly monitor the functional state of synapses in vivo and determine the fate of ischemic terminals. J. Neurosci.29, 3974–3980 (2009). ArticleCASPubMedPubMed Central Google Scholar
Paolicelli, R. C. et al. Synaptic pruning by microglia is necessary for normal brain development. Science333, 1456–1458 (2011). ArticleCASPubMed Google Scholar
Schafer, D. P. et al. Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner. Neuron74, 691–705 (2012). ArticleCASPubMedPubMed Central Google Scholar
Rigato, C., Buckinx, R., Le-Corronc, H., Rigo, J. M. & Legendre, P. Pattern of invasion of the embryonic mouse spinal cord by microglial cells at the time of the onset of functional neuronal networks. Glia59, 675–695 (2011). ArticleCASPubMed Google Scholar
Tremblay, M.-È., Lowery, R. L. & Majewska, A. K. Microglial interactions with synapses are modulated by visual experience. PLoS Biol.8, e1000527 (2010). This paper shows that microglia direct the shaping of dendritic processes by spine removalin vivo. ArticleCASPubMedPubMed Central Google Scholar
Vukovic, J., Colditz, M. J., Blackmore, D. G., Ruitenberg, M. J. & Bartlett, P. F. Microglia modulate hippocampal neural precursor activity in response to exercise and aging. J. Neurosci.32, 6435–6443 (2012). ArticleCASPubMedPubMed Central Google Scholar
Fellner, L. et al. Toll-like receptor 4 is required for α-synuclein dependent activation of microglia and astroglia. Glia61, 349–360 (2013). ArticlePubMedPubMed Central Google Scholar
Stewart, C. R. et al. CD36 ligands promote sterile inflammation through assembly of a Toll-like receptor 4 and 6 heterodimer. Nature Immunol.11, 155–161 (2010). ArticleCAS Google Scholar
Udan, M. L. D., Ajit, D., Crouse, N. R. & Nichols, M. R. Toll-like receptors 2 and 4 mediate Aβ(1–42) activation of the innate immune response in a human monocytic cell line. J. Neurochem.104, 524–533 (2008). CASPubMed Google Scholar
Jin, J.-J., Kim, H.-D., Maxwell, J. A., Li, L. & Fukuchi, K.-I. Toll-like receptor 4-dependent upregulation of cytokines in a transgenic mouse model of Alzheimer's disease. J. Neuroinflamm.5, 23 (2008). ArticleCAS Google Scholar
Latz, E., Xiao, T. S. & Stutz, A. Activation and regulation of the inflammasomes. Nature Rev. Immunol.13, 397–411 (2013). ArticleCAS Google Scholar
Strowig, T., Henao-Mejia, J., Elinav, E. & Flavell, R. Inflammasomes in health and disease. Nature481, 278–286 (2012). ArticleCASPubMed Google Scholar
De Rivero Vaccari, J. P. et al. Therapeutic neutralization of the NLRP1 inflammasome reduces the innate immune response and improves histopathology after traumatic brain injury. J. Cereb. Blood Flow Metab.29, 1251–1261 (2009). ArticleCASPubMedPubMed Central Google Scholar
Adamczak, S. E. et al. Pyroptotic neuronal cell death mediated by the AIM2 inflammasome. J. Cereb. Blood Flow Metab.34, 621–629 (2014). ArticleCASPubMedPubMed Central Google Scholar
Minkiewicz, J., de Rivero Vaccari, J. P. & Keane, R. W. Human astrocytes express a novel NLRP2 inflammasome. Glia61, 1113–1121 (2013). ArticlePubMed Google Scholar
Shimohama, S. et al. Activation of NADPH oxidase in Alzheimer's disease brains. Biochem. Biophys. Res. Commun.273, 5–9 (2000). ArticleCASPubMed Google Scholar
Reynolds, W. F. et al. Myeloperoxidase polymorphism is associated with gender specific risk for Alzheimer's disease. Exp. Neurol.155, 31–41 (1999). ArticleCASPubMed Google Scholar
Heneka, M. T. et al. Neuronal and glial coexpression of argininosuccinate synthetase and inducible nitric oxide synthase in Alzheimer disease. J. Neuropathol. Exp. Neurol.60, 906–916 (2001). ArticleCASPubMed Google Scholar
Vodovotz, Y. et al. Inducible nitric oxide synthase in tangle-bearing neurons of patients with Alzheimer's disease. J. Exp. Med.184, 1425–1433 (1996). ArticleCASPubMed Google Scholar
Monje, M. L., Toda, H. & Palmer, T. D. Inflammatory blockade restores adult hippocampal neurogenesis. Science302, 1760–1765 (2003). ArticleCASPubMed Google Scholar
Nagatsu, T. & Sawada, M. Inflammatory process in Parkinson's disease: role for cytokines. Curr. Pharm. Des.11, 999–1016 (2005). ArticleCASPubMed Google Scholar
Alirezaei, M., Kiosses, W. B., Flynn, C. T., Brady, N. R. & Fox, H. S. Disruption of neuronal autophagy by infected microglia results in neurodegeneration. PLoS ONE3, e2906 (2008). ArticleCASPubMedPubMed Central Google Scholar
Koenigsknecht-Talboo, J. & Landreth, G. E. Microglial phagocytosis induced by fibrillar β-amyloid and IgGs are differentially regulated by proinflammatory cytokines. J. Neurosci.25, 8240–8249 (2005). ArticleCASPubMedPubMed Central Google Scholar
Sheng, J. G. et al. Lipopolysaccharide-induced-neuroinflammation increases intracellular accumulation of amyloid precursor protein and amyloid-β peptide in APPswe transgenic mice. Neurobiol. Dis.14, 133–145 (2003). ArticleCASPubMed Google Scholar
Qiao, X., Cummins, D. J. & Paul, S. M. Neuroinflammation-induced acceleration of amyloid deposition in the APPV717F transgenic mouse. Eur. J. Neurosci.14, 474–482 (2001). ArticleCASPubMed Google Scholar
Jack, C. R. Jr et al. Tracking pathophysiological processes in Alzheimer's disease: an updated hypothetical model of dynamic biomarkers. Lancet Neurol.12, 207–216 (2013). ArticleCASPubMedPubMed Central Google Scholar
Bertram, L., Lill, C. M. & Tanzi, R. E. The genetics of Alzheimer disease: back to the future. Neuron68, 270–281 (2010). ArticleCASPubMed Google Scholar
Mawuenyega, K. G. et al. Decreased clearance of CNS β-amyloid in Alzheimer's disease. Science330, 1774–1774 (2010). This study provides important evidence that the defective clearance of amyloid-β has a pathogenic role in sporadic Alzheimer's disease. ArticleCASPubMedPubMed Central Google Scholar
Breitner, J. C. The role of anti-inflammatory drugs in the prevention and treatment of Alzheimer's disease. Annu. Rev. Med.47, 401–411 (1996). ArticleCASPubMed Google Scholar
Sastre, M. et al. Nonsteroidal anti-inflammatory drugs and peroxisome proliferator-activated receptor-γ agonists modulate immunostimulated processing of amyloid precursor protein through regulation of β-secretase. J. Neurosci.23, 9796–9804 (2003). ArticleCASPubMedPubMed Central Google Scholar
Weggen, S. et al. A subset of NSAIDs lower amyloidogenic Aβ42 independently of cyclooxygenase activity. Nature414, 212–216 (2001). ArticleCASPubMed Google Scholar
in t' Veld, B. A. et al. Nonsteroidal antiinflammatory drugs and the risk of Alzheimer's disease. N. Engl. J. Med.345, 1515–1521 (2001). ArticleCASPubMed Google Scholar
Iwashyna, T. J., Ely, E. W., Smith, D. M. & Langa, K. M. Long-term cognitive impairment and functional disability among survivors of severe sepsis. JAMA304, 1787–1794 (2010). ArticleCASPubMedPubMed Central Google Scholar
Semmler, A. et al. Persistent cognitive impairment, hippocampal atrophy and EEG changes in sepsis survivors. J. Neurol. Neurosurg. Psychiatr.84, 62–69 (2012). Article Google Scholar
Whitmer, R. A., Gunderson, E. P., Quesenberry, C. P. Jr, Zhou, J. & Yaffe, K. Body mass index in midlife and risk of Alzheimer disease and vascular dementia. Curr. Alzheimer Res.4, 103–109 (2007). ArticleCASPubMed Google Scholar
Larson, E. B. et al. Exercise is associated with reduced risk for incident dementia among persons 65 years of age and older. Ann. Intern. Med.144, 73–81 (2006). ArticlePubMed Google Scholar
Kamer, A. R. et al. TNF-α and antibodies to periodontal bacteria discriminate between Alzheimer's disease patients and normal subjects. J. Neuroimmunol.216, 92–97 (2009). ArticleCASPubMedPubMed Central Google Scholar
Kamer, A. R. et al. Inflammation and Alzheimer's disease: possible role of periodontal diseases. Alzheimers Dement.4, 242–250 (2008). ArticleCASPubMed Google Scholar
Sparks Stein, P. et al. Serum antibodies to periodontal pathogens are a risk factor for Alzheimer's disease. Alzheimers Dement.8, 196–203 (2012). ArticleCASPubMed Google Scholar
Cagnin, A. et al. In-vivo measurement of activated microglia in dementia. Lancet358, 461–467 (2001). ArticleCASPubMed Google Scholar
Yasuno, F. et al. Increased binding of peripheral benzodiazepine receptor in mild cognitive impairment-dementia converters measured by positron emission tomography with [11C]DAA1106. Psychiatry Res.203, 67–74 (2012). ArticleCASPubMed Google Scholar
Zhang, B. et al. Integrated systems approach identifies genetic nodes and networks in late-onset Alzheimer's disease. Cell153, 707–720 (2013). This study shows that innate immune networks are associated with Alzheimer's disease. ArticleCASPubMedPubMed Central Google Scholar
Lambert, J.-C. et al. Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease. Nature Genet.41, 1094–1099 (2009). ArticleCASPubMed Google Scholar
Hollingworth, P. et al. Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease. Nature Genet.43, 429–435 (2011). ArticleCASPubMed Google Scholar
Liang, Y. & Tedder, T. F. Identification of a CD20-, FcɛRIβ-, and HTm4-related gene family: sixteen new MS4A family members expressed in human and mouse. Genomics72, 119–127 (2001). ArticleCASPubMed Google Scholar
Lajaunias, F., Dayer, J.-M. & Chizzolini, C. Constitutive repressor activity of CD33 on human monocytes requires sialic acid recognition and phosphoinositide 3-kinase-mediated intracellular signaling. Eur. J. Immunol.35, 243–251 (2005). ArticleCASPubMed Google Scholar
Bradshaw, E. M. et al. CD33 Alzheimer's disease locus: altered monocyte function and amyloid biology. Nature Neurosci.16, 848–850 (2013). This paper shows that a single nucleotide polymorphism in theCD33gene is associated with Alzheimer's disease, and that it leads to altered phagocytosis of amyloid-β fibrils by monocytes and increased levels of amyloid-β in the brains of homozygous carriers. ArticleCASPubMed Google Scholar
Guerreiro, R. et al. TREM2 variants in Alzheimer's disease. N. Engl. J. Med.368, 117–127 (2013). ArticleCASPubMed Google Scholar
Jonsson, T. et al. Variant of TREM2 associated with the risk of Alzheimer's disease. N. Engl. J. Med.368, 107–116 (2013). References 57 and 58 link mutations in the gene that encodes the innate immune receptor TREM2 to rare forms of Alzheimer's disease. ArticleCASPubMed Google Scholar
Frank, S. et al. TREM2 is upregulated in amyloid plaque-associated microglia in aged APP23 transgenic mice. Glia56, 1438–1447 (2008). ArticlePubMed Google Scholar
Melchior, B. et al. Dual induction of TREM2 and tolerance-related transcript, Tmem176b, in amyloid transgenic mice: implications for vaccine-based therapies for Alzheimer's disease. ASN Neuro.2, e00037 (2010). ArticleCASPubMedPubMed Central Google Scholar
Bouchon, A., Hernández-Munain, C., Cella, M. & Colonna, M. A. DAP12-mediated pathway regulates expression of CC chemokine receptor 7 and maturation of human dendritic cells. J. Exp. Med.194, 1111–1122 (2001). ArticleCASPubMedPubMed Central Google Scholar
Hamerman, J. A. et al. Cutting edge: inhibition of TLR and FcR responses in macrophages by triggering receptor expressed on myeloid cells (TREM)-2 and DAP12. J. Immunol.177, 2051–2055 (2006). ArticleCASPubMed Google Scholar
Sheedy, F. J. et al. CD36 coordinates NLRP3 inflammasome activation by facilitating the intracellular nucleation from soluble to particulate ligands in sterile inflammation. Nature Immunol.14, 812–820 (2013). ArticleCAS Google Scholar
Epstein, E. A. & Chapman, M. R. Polymerizing the fibre between bacteria and host cells: the biogenesis of functional amyloid fibres. Cell. Microbiol.10, 1413–1420 (2008). ArticleCASPubMedPubMed Central Google Scholar
Hammer, N. D. et al. The C-terminal repeating units of CsgB direct bacterial functional amyloid nucleation. J. Mol. Biol.422, 376–389 (2012). ArticleCASPubMedPubMed Central Google Scholar
Halle, A. et al. The NALP3 inflammasome is involved in the innate immune response to amyloid-β. Nature Immunol.9, 857–865 (2008). This study shows for the first time that the NLRP3 inflammasome can be activated by fibrillar amyloid-β. ArticleCAS Google Scholar
Heneka, M. T. et al. NLRP3 is activated in Alzheimer's disease and contributes to pathology in APP/PS1 mice. Nature493, 674–678 (2013). This study shows that NLRP3 activation occurs in microglial cells in the brains of patients with Alzheimer's disease and provides evidence that inhibition of NLRP3 protects neuronal cell function and integrityin vivo. ArticleCASPubMed Google Scholar
Tong, L. et al. Brain-derived neurotrophic factor-dependent synaptic plasticity is suppressed by interleukin-1β via p38 mitogen-activated protein kinase. J. Neurosci.32, 17714–17724 (2012). ArticleCASPubMedPubMed Central Google Scholar
Cameron, B. et al. Loss of interleukin receptor-associated kinase 4 signaling suppresses amyloid pathology and alters microglial phenotype in a mouse model of Alzheimer's disease. J. Neurosci.32, 15112–15123 (2012). ArticleCASPubMedPubMed Central Google Scholar
Davalos, D. et al. ATP mediates rapid microglial response to local brain injury in vivo. Nature Neurosci.8, 752–758 (2005). ArticleCASPubMed Google Scholar
Wu, Z. et al. Differential pathways for interleukin-1β production activated by chromogranin A and amyloid-β in microglia. Neurobiol. Aging34, 2715–2725 (2013). ArticleCASPubMed Google Scholar
Shepherd, C. E. et al. Inflammatory S100A9 and S100A12 proteins in Alzheimer's disease. Neurobiol. Aging27, 1554–1563 (2006). ArticleCASPubMed Google Scholar
Kummer, M. P. et al. Mrp14 deficiency ameliorates amyloid-β burden by increasing microglial phagocytosis and modulation of amyloid precursor protein processing. J. Neurosci.32, 17824–17829 (2012). ArticleCASPubMedPubMed Central Google Scholar
Vom Berg, J. et al. Inhibition of IL-12/IL-23 signaling reduces Alzheimer's disease-like pathology and cognitive decline. Nature Med.18, 1812–1819 (2012). This study shows that modulation of the IL-12–IL-23 pathway provides therapeutic benefits in an animal model of cerebral amyloidosis. ArticleCASPubMed Google Scholar
Terwel, D. et al. Critical role of astroglial apolipoprotein E and liver X receptor-α expression for microglial Aβ phagocytosis. J. Neurosci.31, 7049–7059 (2011). ArticleCASPubMedPubMed Central Google Scholar
Kummer, M. P. et al. Nitration of tyrosine 10 critically enhances amyloid-β aggregation and plaque formation. Neuron71, 833–844 (2011). This paper links immune activation and the expression of iNOS to the nitration of amyloid-β and the subsequent formation of plaques. ArticleCASPubMed Google Scholar
Serrano-Pozo, A., Gómez-Isla, T., Growdon, J. H., Frosch, M. P. & Hyman, B. T. A phenotypic change but not proliferation underlies glial responses in Alzheimer disease. Am. J. Pathol.182, 2332–2344 (2013). ArticleCASPubMedPubMed Central Google Scholar
El Khoury, J. et al. Ccr2 deficiency impairs microglial accumulation and accelerates progression of Alzheimer-like disease. Nature Med.13, 432–438 (2007). ArticleCASPubMed Google Scholar
Mildner, A. et al. Distinct and non-redundant roles of microglia and myeloid subsets in mouse models of Alzheimer's disease. J. Neurosci.31, 11159–11171 (2011). ArticleCASPubMedPubMed Central Google Scholar
Kitazawa, M., Oddo, S., Yamasaki, T. R., Green, K. N. & LaFerla, F. M. Lipopolysaccharide-induced inflammation exacerbates tau pathology by a cyclin-dependent kinase 5-mediated pathway in a transgenic model of Alzheimer's disease. J. Neurosci.25, 8843–8853 (2005). ArticleCASPubMedPubMed Central Google Scholar
Lee, C. Y. D. & Landreth, G. E. The role of microglia in amyloid clearance from the AD brain. J. Neural Transm.117, 949–960 (2010). ArticleCASPubMed Google Scholar
Yoshiyama, Y. et al. Synapse loss and microglial activation precede tangles in a P301S tauopathy mouse model. Neuron53, 337–351 (2007). ArticleCASPubMed Google Scholar
Bhaskar, K. et al. Regulation of tau pathology by the microglial fractalkine receptor. Neuron68, 19–31 (2010). This study shows that phosphorylation of endogenous mouse tau occurs in response to LPS challenge and that this phenomenon depends on the expression of IL-1 and TLR4 by microglial cells. ArticleCASPubMedPubMed Central Google Scholar
Van Langenhove, T., van der Zee, J. & Van Broeckhoven, C. The molecular basis of the frontotemporal lobar degeneration-amyotrophic lateral sclerosis spectrum. Ann. Med.44, 817–828 (2012). ArticleCASPubMedPubMed Central Google Scholar
Mackenzie, I. R. A. et al. Nomenclature and nosology for neuropathologic subtypes of frontotemporal lobar degeneration: an update. Acta Neuropathol.119, 1–4 (2010). ArticlePubMed Google Scholar
Sjögren, M., Folkesson, S., Blennow, K. & Tarkowski, E. Increased intrathecal inflammatory activity in frontotemporal dementia: pathophysiological implications. J. Neurol. Neurosurg. Psychiatr.75, 1107–1111 (2004). Article Google Scholar
Cagnin, A., Rossor, M., Sampson, E. L., Mackinnon, T. & Banati, R. B. In vivo detection of microglial activation in frontotemporal dementia. Ann. Neurol.56, 894–897 (2004). ArticlePubMed Google Scholar
Rayaprolu, S. et al. TREM2 in neurodegeneration: evidence for association of the p.R47H variant with frontotemporal dementia and Parkinson's disease. Mol. Neurodegener.8, 19 (2013). ArticleCASPubMedPubMed Central Google Scholar
Baker, M. et al. Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17. Nature442, 916–919 (2006). ArticleCASPubMed Google Scholar
Petkau, T. L. et al. Progranulin expression in the developing and adult murine brain. J. Comp. Neurol.518, 3931–3947 (2010). ArticlePubMed Google Scholar
Chen-Plotkin, A. S. et al. Brain progranulin expression in _GRN_-associated frontotemporal lobar degeneration. Acta Neuropathol.119, 111–122 (2010). ArticleCASPubMed Google Scholar
Kleinberger, G., Capell, A., Haass, C. & Van Broeckhoven, C. Mechanisms of granulin deficiency: lessons from cellular and animal models. Mol. Neurobiol.47, 337–360 (2013). ArticleCASPubMed Google Scholar
Pickford, F. et al. Progranulin is a chemoattractant for microglia and stimulates their endocytic activity. Am. J. Pathol.178, 284–295 (2011). ArticleCASPubMedPubMed Central Google Scholar
Martens, L. H. et al. Progranulin deficiency promotes neuroinflammation and neuron loss following toxin-induced injury. J. Clin. Invest.122, 3955–3959 (2012). ArticleCASPubMedPubMed Central Google Scholar
Yin, F. et al. Exaggerated inflammation, impaired host defense, and neuropathology in progranulin-deficient mice. J. Exp. Med.207, 117–128 (2010). ArticleCASPubMedPubMed Central Google Scholar
Hosler, B. A. et al. Linkage of familial amyotrophic lateral sclerosis with frontotemporal dementia to chromosome 9q21–q22. JAMA284, 1664–1669 (2000). ArticleCASPubMed Google Scholar
Petkau, T. L. et al. Synaptic dysfunction in progranulin-deficient mice. Neurobiol. Dis.45, 711–722 (2012). ArticleCASPubMed Google Scholar
Gerhard, A. et al. [11C](R)-PK11195 PET imaging of microglial activation in multiple system atrophy. Neurology61, 686–689 (2003). ArticleCASPubMed Google Scholar
Mogi, M. et al. Interleukin-1β, interleukin-6, epidermal growth factor and transforming growth factor-α are elevated in the brain from parkinsonian patients. Neurosci. Lett.180, 147–150 (1994). ArticleCASPubMed Google Scholar
Damier, P., Hirsch, E. C., Zhang, P., Agid, Y. & Javoy-Agid, F. Glutathione peroxidase, glial cells and Parkinson's disease. Neuroscience52, 1–6 (1993). ArticleCASPubMed Google Scholar
Hirsch, E. C. & Hunot, S. Neuroinflammation in Parkinson's disease: a target for neuroprotection? Lancet Neurol.8, 382–397 (2009). ArticleCASPubMed Google Scholar
Hamza, T. H. et al. Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson's disease. Nature Genet.42, 781–785 (2010). ArticleCASPubMed Google Scholar
International Parkinson Disease Genomics Consortium. Imputation of sequence variants for identification of genetic risks for Parkinson's disease: a meta-analysis of genome-wide association studies. Lancet377, 641–649 (2011).
McCoy, M. K. et al. Intranigral lentiviral delivery of dominant negative TNF attenuates neurodegeneration and behavioral deficits in hemiparkinsonian rats. Mol. Ther.16, 1572–1579 (2008). ArticleCASPubMedPubMed Central Google Scholar
Zhang, W. et al. Aggregated α-synuclein activates microglia: a process leading to disease progression in Parkinson's disease. FASEB J.19, 533–542 (2005). ArticleCASPubMed Google Scholar
Wu, D.-C. et al. NADPH oxidase mediates oxidative stress in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease. Proc. Natl Acad. Sci. USA100, 6145–6150 (2003). ArticleCASPubMed Google Scholar
Hunot, S. et al. Nitric oxide synthase and neuronal vulnerability in Parkinson's disease. Neuroscience72, 355–363 (1996). ArticleCASPubMed Google Scholar
Giasson, B. I. et al. Oxidative damage linked to neurodegeneration by selective α-synuclein nitration in synucleinopathy lesions. Science290, 985–989 (2000). ArticleCASPubMed Google Scholar
Shavali, S., Combs, C. K. & Ebadi, M. Reactive macrophages increase oxidative stress and alpha-synuclein nitration during death of dopaminergic neuronal cells in co-culture: relevance to Parkinson's disease. Neurochem. Res.31, 85–94 (2006). ArticleCASPubMed 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
Theodore, S., Cao, S., McLean, P. J. & Standaert, D. G. Targeted overexpression of human alpha-synuclein triggers microglial activation and an adaptive immune response in a mouse model of Parkinson disease. J. Neuropathol. Exp. Neurol.67, 1149–1158 (2008). ArticleCASPubMedPubMed Central Google Scholar
Harms, A. S. et al. MHCII is required for α-synuclein-induced activation of microglia, CD4 T cell proliferation, and dopaminergic neurodegeneration. J. Neurosci.33, 9592–9600 (2013). ArticleCASPubMedPubMed Central Google Scholar
Codolo, G. et al. Triggering of inflammasome by aggregated α-synuclein, an inflammatory response in synucleinopathies. PLoS ONE8, e55375 (2013). ArticleCASPubMedPubMed Central Google Scholar
Kawamata, T., Akiyama, H., Yamada, T. & McGeer, P. L. Immunologic reactions in amyotrophic lateral sclerosis brain and spinal cord tissue. Am. J. Pathol.140, 691–707 (1992). CASPubMedPubMed Central Google Scholar
Frakes, A. E. et al. Microglia induce motor neuron death via the classical NF-κB pathway in amyotrophic lateral sclerosis. Neuron81, 1009–1023 (2014). ArticleCASPubMedPubMed Central Google Scholar
Brettschneider, J. et al. Microglial activation correlates with disease progression and upper motor neuron clinical symptoms in amyotrophic lateral sclerosis. PLoS ONE7, e39216 (2012). ArticleCASPubMedPubMed Central Google Scholar
Boillée, S. et al. Onset and progression in inherited ALS determined by motor neurons and microglia. Science312, 1389–1392 (2006). This paper shows that microglial cell-restricted deficiency of mutant SOD1 in the SODG93Amouse model of amyotrophic lateral sclerosis causes prolonged survival in mice, thus proving a role for microglia in disease progression. ArticleCASPubMed Google Scholar
Clement, A. M. et al. Wild-type nonneuronal cells extend survival of SOD1 mutant motor neurons in ALS mice. Science302, 113–117 (2003). ArticleCASPubMed Google Scholar
Yamanaka, K. et al. Astrocytes as determinants of disease progression in inherited amyotrophic lateral sclerosis. Nature Neurosci.11, 251–253 (2008). ArticleCASPubMed Google Scholar
Meissner, F., Molawi, K. & Zychlinsky, A. Mutant superoxide dismutase 1-induced IL-1β accelerates ALS pathogenesis. Proc. Natl Acad. Sci. USA107, 13046–13050 (2010). ArticlePubMed Google Scholar
Iłzecka, J., Stelmasiak, Z. & Dobosz, B. Interleukin-1β converting enzyme/Caspase-1 (ICE/Caspase-1) and soluble APO-1/Fas/CD 95 receptor in amyotrophic lateral sclerosis patients. Acta Neurol. Scand.103, 255–258 (2001). ArticlePubMed Google Scholar
Pasinelli, P., Borchelt, D. R., Houseweart, M. K., Cleveland, D. W. & Brown, R. H. Jr. Caspase-1 is activated in neural cells and tissue with amyotrophic lateral sclerosis-associated mutations in copper-zinc superoxide dismutase. Proc. Natl Acad. Sci. USA95, 15763–15768 (1998). ArticleCASPubMed Google Scholar
Han, P. & Whelan, P. J. Tumor necrosis factor alpha enhances glutamatergic transmission onto spinal motoneurons. J. Neurotrauma27, 287–292 (2010). ArticlePubMed Google Scholar
Sargsyan, S. A. et al. A comparison of in vitro properties of resting SOD1 transgenic microglia reveals evidence of reduced neuroprotective function. BMC Neurosci.12, 91 (2011). ArticleCASPubMedPubMed Central Google Scholar
Nguyen, M. D., D'Aigle, T., Gowing, G., Julien, J.-P. & Rivest, S. Exacerbation of motor neuron disease by chronic stimulation of innate immunity in a mouse model of amyotrophic lateral sclerosis. J. Neurosci.24, 1340–1349 (2004). ArticleCASPubMedPubMed Central Google Scholar
Kiaei, M., Kipiani, K., Chen, J., Calingasan, N. Y. & Beal, M. F. Peroxisome proliferator-activated receptor-gamma agonist extends survival in transgenic mouse model of amyotrophic lateral sclerosis. Exp. Neurol.191, 331–336 (2005). 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). ArticleCASPubMedPubMed Central Google Scholar
Dupuis, L. et al. A randomized, double blind, placebo-controlled trial of pioglitazone in combination with riluzole in amyotrophic lateral sclerosis. PLoS ONE7, e37885 (2012). ArticleCASPubMedPubMed Central Google Scholar
Wilcock, G. K. et al. Efficacy and safety of tarenflurbil in mild to moderate Alzheimer's disease: a randomised phase II trial. Lancet Neurol.7, 483–493 (2008). ArticleCASPubMed Google Scholar
Levine, T. D. et al. A pilot trial of pioglitazone HCl and tretinoin in ALS: cerebrospinal fluid biomarkers to monitor drug efficacy and predict rate of disease progression. Neurol. Res. Int.2012, 1–6 (2012). Article Google Scholar
Singhrao, S. K., Neal, J. W., Morgan, B. P. & Gasque, P. Increased complement biosynthesis by microglia and complement activation on neurons in Huntington's disease. Exp. Neurol.159, 362–376 (1999). ArticleCASPubMed Google Scholar
Ona, V. O. et al. Inhibition of caspase-1 slows disease progression in a mouse model of Huntington's disease. Nature399, 263–267 (1999). ArticleCASPubMed Google Scholar
Dalrymple, A. et al. Proteomic profiling of plasma in Huntington's disease reveals neuroinflammatory activation and biomarker candidates. J. Proteome Res.6, 2833–2840 (2007). ArticleCASPubMed Google Scholar
Björkqvist, M. et al. A novel pathogenic pathway of immune activation detectable before clinical onset in Huntington's disease. J. Exp. Med.205, 1869–1877 (2008). ArticleCASPubMedPubMed Central Google Scholar
Silvestroni, A., Faull, R. L. M., Strand, A. D. & Möller, T. Distinct neuroinflammatory profile in post-mortem human Huntington's disease. Neuroreport20, 1098–1103 (2009). ArticlePubMed Google Scholar
Tai, Y. F. et al. Microglial activation in presymptomatic Huntington's disease gene carriers. Brain130, 1759–1766 (2007). ArticlePubMed Google Scholar
Simmons, D. A. et al. Ferritin accumulation in dystrophic microglia is an early event in the development of Huntington's disease. Glia55, 1074–1084 (2007). ArticlePubMed Google Scholar
Crotti, A. et al. Mutant Huntingtin promotes autonomous microglia activation via myeloid lineage-determining factors. Nature Neurosci.17, 513–521 (2014). ArticleCASPubMed Google Scholar
Crocker, S. F., Costain, W. J. & Robertson, H. A. DNA microarray analysis of striatal gene expression in symptomatic transgenic Huntington's mice (R6/2) reveals neuroinflammation and insulin associations. Brain Res.1088, 176–186 (2006). ArticleCASPubMed Google Scholar
Kraft, A. D., Kaltenbach, L. S., Lo, D. C. & Harry, G. J. Activated microglia proliferate at neurites of mutant huntingtin-expressing neurons. Neurobiol. Aging33, 621.e17–621.e33 (2012). ArticleCAS Google Scholar
Khoshnan, A. et al. Activation of the IκB kinase complex and nuclear factor-κB contributes to mutant huntingtin neurotoxicity. J. Neurosci.24, 7999–8008 (2004). ArticleCASPubMedPubMed Central Google Scholar
Palazuelos, J. et al. Microglial CB2 cannabinoid receptors are neuroprotective in Huntington's disease excitotoxicity. Brain132, 3152–3164 (2009). ArticlePubMed Google Scholar
Bradford, J. et al. Expression of mutant huntingtin in mouse brain astrocytes causes age-dependent neurological symptoms. PNAS106, 22480–22485 (2009). ArticlePubMed Google Scholar
Shin, J.-Y. et al. Expression of mutant huntingtin in glial cells contributes to neuronal excitotoxicity. J. Cell Biol.171, 1001–1012 (2005). ArticleCASPubMedPubMed Central Google Scholar
Richards, R. I., Samaraweera, S. E., van Eyk, C. L., O'Keefe, L. V. & Suter, C. M. RNA pathogenesis via Toll-like receptor-activated inflammation in expanded repeat neurodegenerative diseases. Front. Mol. Neurosci.6, 25 (2013). ArticlePubMedPubMed Central Google Scholar
Samaraweera, S. E., O'Keefe, L. V., Price, G. R., Venter, D. J. & Richards, R. I. Distinct roles for Toll and autophagy pathways in double-stranded RNA toxicity in a Drosophila model of expanded repeat neurodegenerative diseases. Hum. Mol. Genet.22, 2811–2819 (2013). This study provides the first evidence for a role of dsRNA in mediating the activation of innate immunity in neurodegenerative diseases that are caused by the expansion of variable copy number, tandem repeat sequences. ArticleCASPubMedPubMed Central Google Scholar
Shepherd, C. E., Thiel, E., McCann, H., Harding, A. J. & Halliday, G. M. Cortical inflammation in Alzheimer disease but not dementia with Lewy bodies. Arch. Neurol.57, 817–822 (2000). ArticleCASPubMed Google Scholar
Mackenzie, I. R. Activated microglia in dementia with Lewy bodies. Neurology55, 132–134 (2000). ArticleCASPubMed Google Scholar
Katsuse, O., Iseki, E. & Kosaka, K. Immunohistochemical study of the expression of cytokines and nitric oxide synthases in brains of patients with dementia with Lewy bodies. Neuropathology23, 9–15 (2003). ArticlePubMed Google Scholar
Rozemuller, A. J., Eikelenboom, P., Theeuwes, J. W., Jansen Steur, E. N. & de Vos, R. A. Activated microglial cells and complement factors are unrelated to cortical Lewy bodies. Acta Neuropathol.100, 701–708 (2000). ArticleCASPubMed Google Scholar
Rüb, U. et al. The nucleus raphe interpositus in spinocerebellar ataxia type 3 (Machado–Joseph disease). J. Chem. Neuroanat.25, 115–127 (2003). ArticleCASPubMed Google Scholar
Petersen, A. J., Rimkus, S. A. & Wassarman, D. A. ATM kinase inhibition in glial cells activates the innate immune response and causes neurodegeneration in Drosophila. Proc. Natl Acad. Sci. USA109, E656–E664 (2012). ArticlePubMed Google Scholar
Petersen, A. J., Katzenberger, R. J. & Wassarman, D. A. The innate immune response transcription factor relish is necessary for neurodegeneration in a Drosophila model of ataxia-telangiectasia. Genetics194, 133–142 (2013). ArticleCASPubMedPubMed Central Google Scholar
Hsiao, K. et al. Correlative memory deficits, Aβ elevation, and amyloid plaques in transgenic mice. Science274, 99–102 (1996). ArticleCASPubMed Google Scholar
Jankowsky, J. L. et al. Co-expression of multiple transgenes in mouse CNS: a comparison of strategies. Biomol. Eng.17, 157–165 (2001). ArticleCASPubMed Google Scholar
Jackson-Lewis, V. & Przedborski, S. Protocol for the MPTP mouse model of Parkinson's disease. Nature Protocols2, 141–151 (2007). ArticleCASPubMed Google Scholar
Ungerstedt, U. 6-Hydroxy-dopamine induced degeneration of central monoamine neurons. Eur. J. Pharmacol.5, 107–110 (1968). ArticleCASPubMed Google Scholar
St Martin, J. L. et al. Dopaminergic neuron loss and up-regulation of chaperone protein mRNA induced by targeted over-expression of alpha-synuclein in mouse substantia nigra. J. Neurochem.100, 1449–1457 (2007). CASPubMed Google Scholar
Gurney, M. E. et al. Motor neuron degeneration in mice that express a human Cu, Zn superoxide dismutase mutation. Science264, 1772–1775 (1994). ArticleCASPubMed Google Scholar
Wong, P. C. et al. An adverse property of a familial ALS-linked SOD1 mutation causes motor neuron disease characterized by vacuolar degeneration of mitochondria. Neuron14, 1105–1116 (1995). ArticleCASPubMed Google Scholar
Mangiarini, L. et al. Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice. Cell87, 493–506 (1996). ArticleCASPubMed Google Scholar