Withaferin A Induces Heat Shock Response and Ameliorates Disease Progression in a Mouse Model of Huntington’s Disease (original) (raw)

References

1. Mendez MF (1994) Huntington’s disease: update and review of neuropsychiatric aspects. Int J Psychiatry Med 24(3):189–208. https://doi.org/10.2190/HU6W-3K7Q-NAEL-XU6K
   Article CAS PubMed Google Scholar
2. Bates GP, Dorsey R, Gusella JF, Hayden MR, Kay C, Leavitt BR, Nance M, Ross CA et al (2015) Huntington disease Nat Rev Dis Primers 1:15005. https://doi.org/10.1038/nrdp.2015.5
   Article PubMed Google Scholar
3. The Huntington’s Disease Collaborative Research Group (1993) A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington’s disease chromosomes. Cell 72(6):971–983. https://doi.org/10.1016/0092-8674(93)90585-E
   Article Google Scholar
4. Goldberg YP, Nicholson DW, Rasper DM, Kalchman MA, Koide HB, Graham RK, Bromm M, Kazemi-Esfarjani P et al (1996) Cleavage of huntingtin by apopain, a proapoptotic cysteine protease, is modulated by the polyglutamine tract. Nat Genet 13(4):442–449. https://doi.org/10.1038/ng0896-442
   Article CAS PubMed Google Scholar
5. DiFiglia M, Sapp E, Chase KO, Davies SW, Bates GP, Vonsattel JP, Aronin N (1997) Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science 277(5334):1990–1993
   Article CAS Google Scholar
6. Orr HT, Zoghbi HY (2007) Trinucleotide repeat disorders. Annu Rev Neurosci 30:575–621. https://doi.org/10.1146/annurev.neuro.29.051605.113042
   Article CAS PubMed Google Scholar
7. Landles C, Bates GP (2004) Huntingtin and the molecular pathogenesis of Huntington’s disease. Fourth in molecular medicine review series. EMBO Rep 5(10):958–963. https://doi.org/10.1038/sj.embor.7400250
   Article CAS PubMed PubMed Central Google Scholar
8. Hedreen JC, Folstein SE (1995) Early loss of neostriatal striosome neurons in Huntington’s disease. J Neuropathol Exp Neurol 54(1):105–120
   Article CAS Google Scholar
9. Graveland GA, Williams RS, DiFiglia M (1985) Evidence for degenerative and regenerative changes in neostriatal spiny neurons in Huntington’s disease. Science 227(4688):770–773
   Article CAS Google Scholar
10. Vonsattel JP, Myers RH, Stevens TJ, Ferrante RJ, Bird ED, Richardson EP Jr (1985) Neuropathological classification of Huntington’s disease. J Neuropathol Exp Neurol 44(6):559–577
    Article CAS Google Scholar
11. Gatchel JR, Zoghbi HY (2005) Diseases of unstable repeat expansion: mechanisms and common principles. Nat Rev Genet 6(10):743–755. https://doi.org/10.1038/nrg1691
    Article CAS PubMed Google Scholar
12. Lansbury PT, Lashuel HA (2006) A century-old debate on protein aggregation and neurodegeneration enters the clinic. Nature 443(7113):774–779. https://doi.org/10.1038/nature05290
    Article CAS PubMed Google Scholar
13. Margulis J, Finkbeiner S (2014) Proteostasis in striatal cells and selective neurodegeneration in Huntington’s disease. Front Cell Neurosci 8:218. https://doi.org/10.3389/fncel.2014.00218
    Article PubMed PubMed Central Google Scholar
14. Rubinsztein DC, Carmichael J (2003) Huntington’s disease: molecular basis of neurodegeneration. Expert Rev Mol Med 5(20):1–21. https://doi.org/10.1017/S1462399403006549
    Article PubMed Google Scholar
15. Jana NR, Nukina N (2003) Recent advances in understanding the pathogenesis of polyglutamine diseases: involvement of molecular chaperones and ubiquitin-proteasome pathway. J Chem Neuroanat 26(2):95–101
    Article CAS Google Scholar
16. Samant RS, Livingston CM, Sontag EM, Frydman J (2018) Distinct proteostasis circuits cooperate in nuclear and cytoplasmic protein quality control. Nature 563(7731):407–411. https://doi.org/10.1038/s41586-018-0678-x
    Article CAS PubMed PubMed Central Google Scholar
17. Bennett EJ, Shaler TA, Woodman B, Ryu KY, Zaitseva TS, Becker CH, Bates GP, Schulman H et al (2007) Global changes to the ubiquitin system in Huntington’s disease. Nature 448(7154):704–708
    Article CAS Google Scholar
18. Wang J, Wang CE, Orr A, Tydlacka S, Li SH, Li XJ (2008) Impaired ubiquitin-proteasome system activity in the synapses of Huntington’s disease mice. J Cell Biol 180(6):1177–1189
    Article CAS Google Scholar
19. Jana NR, Zemskov EA, Wang G, Nukina N (2001) Altered proteasomal function due to the expression of polyglutamine-expanded truncated N-terminal huntingtin induces apoptosis by caspase activation through mitochondrial cytochrome c release. Hum Mol Genet 10(10):1049–1059
    Article CAS Google Scholar
20. Cortes CJ, La Spada AR (2014) The many faces of autophagy dysfunction in Huntington’s disease: from mechanism to therapy. Drug Discov Today 19(7):963–971
    Article CAS Google Scholar
21. Sarkar S, Ravikumar B, Floto RA, Rubinsztein DC (2009) Rapamycin and mTOR-independent autophagy inducers ameliorate toxicity of polyglutamine-expanded huntingtin and related proteinopathies. Cell Death Differ 16(1):46–56
    Article CAS Google Scholar
22. Rubinsztein DC (2006) The roles of intracellular protein-degradation pathways in neurodegeneration. Nature 443(7113):780–786
    Article CAS Google Scholar
23. Pinho BR, Duarte AI, Canas PM, Moreira PI, Murphy MP, Oliveira JMA (2020) The interplay between redox signalling and proteostasis in neurodegeneration: in vivo effects of a mitochondria-targeted antioxidant in Huntington’s disease mice. Free Radic Biol Med 146:372–382. https://doi.org/10.1016/j.freeradbiomed.2019.11.021
    Article CAS PubMed PubMed Central Google Scholar
24. Ravikumar B, Vacher C, Berger Z, Davies JE, Luo S, Oroz LG, Scaravilli F, Easton DF et al (2004) Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease. Nat Genet 36(6):585–595. https://doi.org/10.1038/ng1362
    Article CAS PubMed Google Scholar
25. Koyuncu S, Saez I, Lee HJ, Gutierrez-Garcia R, Pokrzywa W, Fatima A, Hoppe T, Vilchez D (2018) The ubiquitin ligase UBR5 suppresses proteostasis collapse in pluripotent stem cells from Huntington’s disease patients. Nat Commun 9(1):2886. https://doi.org/10.1038/s41467-018-05320-3
    Article CAS PubMed PubMed Central Google Scholar
26. Soares TR, Reis SD, Pinho BR, Duchen MR, Oliveira JMA (2019) Targeting the proteostasis network in Huntington’s disease. Ageing Res Rev 49:92–103. https://doi.org/10.1016/j.arr.2018.11.006
    Article CAS PubMed PubMed Central Google Scholar
27. Maheshwari M, Bhutani S, Das A, Mukherjee R, Sharma A, Kino Y, Nukina N, Jana NR (2014) Dexamethasone induces heat shock response and slows down disease progression in mouse and fly models of Huntington’s disease. Hum Mol Genet 23(10):2737–2751
    Article CAS Google Scholar
28. Neef DW, Jaeger AM, Thiele DJ (2011) Heat shock transcription factor 1 as a therapeutic target in neurodegenerative diseases. Nat Rev Drug Discov 10(12):930–944
    Article CAS Google Scholar
29. Singh BK, Vatsa N, Nelson VK, Kumar V, Kumar SS, Mandal SC, Pal M, Jana NR (2018) Azadiradione restores protein quality control and ameliorates the disease pathogenesis in a mouse model of Huntington’s disease. Mol Neurobiol 55(8):6337–6346. https://doi.org/10.1007/s12035-017-0853-3
    Article CAS PubMed Google Scholar
30. Gomez-Pastor R, Burchfiel ET, Neef DW, Jaeger AM, Cabiscol E, McKinstry SU, Doss A, Aballay A et al (2017) Abnormal degradation of the neuronal stress-protective transcription factor HSF1 in Huntington’s disease. Nat Commun 8:14405
    Article CAS Google Scholar
31. Chafekar SM, Duennwald ML (2012) Impaired heat shock response in cells expressing full-length polyglutamine-expanded huntingtin. PLoS ONE 7(5):e37929. https://doi.org/10.1371/journal.pone.0037929
    Article CAS PubMed PubMed Central Google Scholar
32. Fujimoto M, Takaki E, Hayashi T, Kitaura Y, Tanaka Y, Inouye S, Nakai A (2005) Active HSF1 significantly suppresses polyglutamine aggregate formation in cellular and mouse models. J Biol Chem 280(41):34908–34916
    Article CAS Google Scholar
33. Sittler A, Lurz R, Lueder G, Priller J, Lehrach H, Hayer-Hartl MK, Hartl FU, Wanker EE (2001) Geldanamycin activates a heat shock response and inhibits huntingtin aggregation in a cell culture model of Huntington’s disease. Hum Mol Genet 10(12):1307–1315
    Article CAS Google Scholar
34. Labbadia J, Cunliffe H, Weiss A, Katsyuba E, Sathasivam K, Seredenina T, Woodman B, Moussaoui S et al (2011) Altered chromatin architecture underlies progressive impairment of the heat shock response in mouse models of Huntington disease. J Clin Invest 121(8):3306–3319
    Article CAS Google Scholar
35. Westerheide SD, Bosman JD, Mbadugha BN, Kawahara TL, Matsumoto G, Kim S, Gu W, Devlin JP et al (2004) Celastrols as inducers of the heat shock response and cytoprotection. J Biol Chem 279(53):56053–56060
    Article CAS Google Scholar
36. Mishra LC, Singh BB, Dagenais S (2000) Scientific basis for the therapeutic use of Withania somnifera (ashwagandha): a review. Altern Med Rev 5(4):334–346
    CAS PubMed Google Scholar
37. Kuboyama T, Tohda C, Komatsu K (2014) Effects of Ashwagandha (roots of Withania somnifera) on neurodegenerative diseases. Biol Pharm Bull 37(6):892–897. https://doi.org/10.1248/bpb.b14-00022
    Article CAS PubMed Google Scholar
38. Swarup V, Phaneuf D, Dupre N, Petri S, Strong M, Kriz J, Julien JP (2011) Deregulation of TDP-43 in amyotrophic lateral sclerosis triggers nuclear factor kappaB-mediated pathogenic pathways. J Exp Med 208(12):2429–2447. https://doi.org/10.1084/jem.20111313
    Article CAS PubMed PubMed Central Google Scholar
39. Patel P, Julien JP, Kriz J (2015) Early-stage treatment with Withaferin A reduces levels of misfolded superoxide dismutase 1 and extends lifespan in a mouse model of amyotrophic lateral sclerosis. Neurotherapeutics 12(1):217–233. https://doi.org/10.1007/s13311-014-0311-0
    Article CAS PubMed Google Scholar
40. Dutta K, Patel P, Julien JP (2018) Protective effects of Withania somnifera extract in SOD1(G93A) mouse model of amyotrophic lateral sclerosis. Exp Neurol 309:193–204. https://doi.org/10.1016/j.expneurol.2018.08.008
    Article CAS PubMed Google Scholar
41. Dutta K, Patel P, Rahimian R, Phaneuf D, Julien JP (2017) Withania somnifera reverses transactive response DNA binding protein 43 proteinopathy in a mouse model of amyotrophic lateral sclerosis/frontotemporal lobar degeneration. Neurotherapeutics 14(2):447–462. https://doi.org/10.1007/s13311-016-0499-2
    Article CAS PubMed Google Scholar
42. Sehgal N, Gupta A, Valli RK, Joshi SD, Mills JT, Hamel E, Khanna P, Jain SC, Thakur SS, Ravindranath V (2012) Withania somnifera reverses Alzheimer’s disease pathology by enhancing low-density lipoprotein receptor-related protein in liver. Proc Natl Acad Sci U S A 109(9):3510–3515. https://doi.org/10.1073/pnas.1112209109
    Article PubMed PubMed Central Google Scholar
43. Santagata S, Xu YM, Wijeratne EM, Kontnik R, Rooney C, Perley CC, Kwon H, Clardy J, Kesari S, Whitesell L, Lindquist S, Gunatilaka AA (2012) Using the heat-shock response to discover anticancer compounds that target protein homeostasis. ACS Chem Biol 7(2):340–349. https://doi.org/10.1021/cb200353m
    Article CAS PubMed Google Scholar
44. Khan S, Rammeloo AW, Heikkila JJ (2012) Withaferin A induces proteasome inhibition, endoplasmic reticulum stress, the heat shock response and acquisition of thermotolerance. PLoS ONE 7(11):e50547. https://doi.org/10.1371/journal.pone.0050547
    Article CAS PubMed PubMed Central Google Scholar
45. Maheshwari M, Shekhar S, Singh BK, Jamal I, Vatsa N, Kumar V, Sharma A, Jana NR (2014) Deficiency of Ube3a in Huntington’s disease mice brain increases aggregate load and accelerates disease pathology. Hum Mol Genet 23(23):6235–6245
    Article CAS Google Scholar
46. Drouin-Ouellet J, Sawiak SJ, Cisbani G, Lagace M, Kuan WL, Saint-Pierre M, Dury RJ, Alata W, St-Amour I, Mason SL, Calon F, Lacroix S, Gowland PA, Francis ST, Barker RA, Cicchetti F (2015) Cerebrovascular and blood-brain barrier impairments in Huntington’s disease: potential implications for its pathophysiology. Ann Neurol 78(2):160–177. https://doi.org/10.1002/ana.24406
    Article PubMed Google Scholar
47. Pido-Lopez J, Tanudjojo B, Farag S, Bondulich MK, Andre R, Tabrizi SJ, Bates GP (2019) Inhibition of tumour necrosis factor alpha in the R6/2 mouse model of Huntington’s disease by etanercept treatment. Sci Rep 9(1):7202. https://doi.org/10.1038/s41598-019-43627-3
    Article CAS PubMed PubMed Central Google Scholar
48. Holmberg CI, Staniszewski KE, Mensah KN, Matouschek A, Morimoto RI (2004) Inefficient degradation of truncated polyglutamine proteins by the proteasome. EMBO J 23(21):4307–4318. https://doi.org/10.1038/sj.emboj.7600426
    Article CAS PubMed PubMed Central Google Scholar
49. Jana NR, Tanaka M, Wang G, Nukina N (2000) Polyglutamine length-dependent interaction of Hsp40 and Hsp70 family chaperones with truncated N-terminal huntingtin: their role in suppression of aggregation and cellular toxicity. Hum Mol Genet 9(13):2009–2018. https://doi.org/10.1093/hmg/9.13.2009
    Article CAS PubMed Google Scholar
50. Hay DG, Sathasivam K, Tobaben S, Stahl B, Marber M, Mestril R, Mahal A, Smith DL, Woodman B, Bates GP (2004) Progressive decrease in chaperone protein levels in a mouse model of Huntington’s disease and induction of stress proteins as a therapeutic approach. Hum Mol Genet 13(13):1389–1405. https://doi.org/10.1093/hmg/ddh144
    Article CAS PubMed Google Scholar
51. Jiang M, Wang J, Fu J, Du L, Jeong H, West T, Xiang L, Peng Q, Hou Z, Cai H, Seredenina T, Arbez N, Zhu S, Sommers K, Qian J, Zhang J, Mori S, Yang XW, Tamashiro KL, Aja S, Moran TH, Luthi-Carter R, Martin B, Maudsley S, Mattson MP, Cichewicz RH, Ross CA, Holtzman DM, Krainc D, Duan W (2011) Neuroprotective role of Sirt1 in mammalian models of Huntington’s disease through activation of multiple Sirt1 targets. Nat Med 18(1):153–158. https://doi.org/10.1038/nm.2558
    Article CAS PubMed PubMed Central Google Scholar
52. Reynolds RH, Petersen MH, Willert CW, Heinrich M, Nymann N, Dall M, Treebak JT, Bjorkqvist M, Silahtaroglu A, Hasholt L, Norremolle A (2018) Perturbations in the p53/miR-34a/SIRT1 pathway in the R6/2 Huntington’s disease model. Mol Cell Neurosci 88:118–129. https://doi.org/10.1016/j.mcn.2017.12.009
    Article CAS PubMed Google Scholar
53. Fujikake N, Nagai Y, Popiel HA, Okamoto Y, Yamaguchi M, Toda T (2008) Heat shock transcription factor 1-activating compounds suppress polyglutamine-induced neurodegeneration through induction of multiple molecular chaperones. J Biol Chem 283(38):26188–26197
    Article CAS Google Scholar
54. Matai L, Sarkar GC, Chamoli M, Malik Y, Kumar SS, Rautela U, Jana NR, Chakraborty K, Mukhopadhyay A (2019) Dietary restriction improves proteostasis and increases life span through endoplasmic reticulum hormesis. Proc Natl Acad Sci U S A 116(35):17383–17392. https://doi.org/10.1073/pnas.1900055116
    Article CAS PubMed PubMed Central Google Scholar
55. Dar NJ, Ahmad Muzamil (2020) Neurodegenerative diseases and Withaniasomnifera (L.): an update. J Ethnopharmacol 256:112769. https://doi.org/10.1016/j.jep.2020.112769
    Article CAS PubMed Google Scholar
56. Kumar S, Phaneuf D, Julien JP (2020) Withaferin-A treatment alleviates TAR DNA-binding protein-43 pathology and improves cognitive function in a mouse model of FTLD. Neurotherapeutics. https://doi.org/10.1007/s13311-020-00952-0
    Article PubMed PubMed Central Google Scholar
57. Heyninck K, Lahtela-Kakkonen M, Van der Veken P, Haegeman G, Vanden Berghe W (2014) Withaferin A inhibits NF-kappaB activation by targeting cysteine 179 in IKKbeta. Biochem Pharmacol 91(4):501–509. https://doi.org/10.1016/j.bcp.2014.08.004
    Article CAS PubMed Google Scholar
58. White PT, Subramanian C, Motiwala HF, Cohen MS (2016) Natural withanolides in the treatment of chronic diseases. Adv Exp Med Biol 928:329–373. https://doi.org/10.1007/978-3-319-41334-1_14
    Article CAS PubMed PubMed Central Google Scholar
59. Bjorkqvist M, Wild EJ, Thiele J, Silvestroni A, Andre R, Lahiri N, Raibon E, Lee RV, Benn CL, Soulet D, Magnusson A, Woodman B, Landles C, Pouladi MA, Hayden MR, Khalili-Shirazi A, Lowdell MW, Brundin P, Bates GP, Leavitt BR, Moller T, Tabrizi SJ (2008) A novel pathogenic pathway of immune activation detectable before clinical onset in Huntington’s disease. J Exp Med 205(8):1869–1877. https://doi.org/10.1084/jem.20080178
    Article CAS PubMed PubMed Central Google Scholar
60. Trager U, Andre R, Lahiri N, Magnusson-Lind A, Weiss A, Grueninger S, McKinnon C, Sirinathsinghji E, Kahlon S, Pfister EL, Moser R, Hummerich H, Antoniou M, Bates GP, Luthi-Carter R, Lowdell MW, Bjorkqvist M, Ostroff GR, Aronin N, Tabrizi SJ (2014) HTT-lowering reverses Huntington’s disease immune dysfunction caused by NFkappaB pathway dysregulation. Brain 137(Pt 3):819–833. https://doi.org/10.1093/brain/awt355
    Article PubMed PubMed Central Google Scholar
61. Valadao PAC, Santos KBS, Ferreira EVTH, Macedo ECT, Teixeira AL, Guatimosim C, de Miranda AS (2020) Inflammation in Huntington’s disease: a few new twists on an old tale. J Neuroimmunol 348:577380. https://doi.org/10.1016/j.jneuroim.2020.577380
    Article CAS PubMed Google Scholar
62. Khoshnan A, Ko J, Watkin EE, Paige LA, Reinhart PH, Patterson PH (2004) Activation of the IkappaB kinase complex and nuclear factor-kappaB contributes to mutant huntingtin neurotoxicity. J Neurosci 24(37):7999–8008. https://doi.org/10.1523/JNEUROSCI.2675-04.2004
    Article CAS PubMed PubMed Central Google Scholar
63. Thompson LM, Aiken CT, Kaltenbach LS, Agrawal N, Illes K, Khoshnan A, Martinez-Vincente M, Arrasate M, O’Rourke JG, Khashwji H, Lukacsovich T, Zhu YZ, Lau AL, Massey A, Hayden MR, Zeitlin SO, Finkbeiner S, Green KN, LaFerla FM, Bates G, Huang L, Patterson PH, Lo DC, Cuervo AM, Marsh JL, Steffan JS (2009) IKK phosphorylates Huntingtin and targets it for degradation by the proteasome and lysosome. J Cell Biol 187(7):1083–1099. https://doi.org/10.1083/jcb.200909067
    Article CAS PubMed PubMed Central Google Scholar
64. Hsiao HY, Chen YC, Chen HM, Tu PH, Chern Y (2013) A critical role of astrocyte-mediated nuclear factor-kappaB-dependent inflammation in Huntington’s disease. Hum Mol Genet 22(9):1826–1842. https://doi.org/10.1093/hmg/ddt036
    Article CAS PubMed Google Scholar
65. Vigont VA, Grekhnev DA, Lebedeva OS, Gusev KO, Volovikov EA, Skopin AY, Bogomazova AN, Shuvalova LD, Zubkova OA, Khomyakova EA, Glushankova LN, Klyushnikov SA, Illarioshkin SN, Lagarkova MA, Kaznacheyeva EV (2021) STIM2 mediates excessive store-operated calcium entry in patient-specific iPSC-derived neurons modeling a juvenile form of Huntington’s disease. Front Cell DevBiol 9:625231. https://doi.org/10.3389/fcell.2021.625231
    Article Google Scholar

Download references