Abstract
Protein folding is a complex, multisystem process characterized by heavy molecular and cellular footprints. Chaperone machinery enables proper protein folding and stable conformation. Other pathways concomitant with the protein folding process include transcription, translation, post-translational modifications, degradation through the ubiquitin-proteasome system, and autophagy. As such, the folding process can go awry in several different ways. The pathogenic basis behind most neurodegenerative diseases is that the disruption of protein homeostasis (i.e. proteostasis) at any level will eventually lead to protein misfolding. Misfolded proteins often aggregate and accumulate to trigger neurotoxicity through cellular stress pathways and consequently cause neurodegenerative diseases. The manifestation of a disease is usually dependent on the specific brain region that the neurotoxicity affects. Neurodegenerative diseases are age-associated, and their incidence is expected to rise as humans continue to live longer and pursue a greater life expectancy. We presently review the sequelae of protein misfolding and aggregation, as well as the role of these phenomena in several neurodegenerative diseases including Alzheimer’s disease, Huntington’s disease, amyotrophic lateral sclerosis, Parkinson’s disease, transmissible spongiform encephalopathies, and spinocerebellar ataxia. Strategies for treatment and therapy are also conferred with respect to impairing, inhibiting, or reversing protein misfolding.
Acknowledgments
The authors are thankful to Drs. Kelly Warren, Inefta Reid, Todd Miller, and Peter Brink for departmental support, as well as to Mrs. Wendy Isser and Ms. Grace Garey for literature retrieval.
Conflict of interest statement: The authors have no conflicts of interest to declare.
References
Alzheimer’s, A. (2015). 2015 Alzheimer’s disease facts and figures. Alzheimers Dement. 11, 332–384.10.1016/j.jalz.2015.02.003Search in Google Scholar
Andersen, J.K. (2004). Oxidative stress in neurodegeneration: cause or consequence? Nat. Med. 10 (Suppl), S18–S25.10.1038/nrn1434Search in Google Scholar
Balch, W.E., Morimoto, R.I., Dillin, A., and Kelly, J.W. (2008). Adapting proteostasis for disease intervention. Science 319, 916–919.10.1126/science.1141448Search in Google Scholar
Baranczak, A. and Kelly, J.W. (2016). A current pharmacologic agent versus the promise of next generation therapeutics to ameliorate protein misfolding and/or aggregation diseases. Curr. Opin. Chem. Biol. 32, 10–21.10.1016/j.cbpa.2016.01.009Search in Google Scholar
Barral, J.M., Broadley, S.A., Schaffar, G., and Hartl, F.U. (2004). Roles of molecular chaperones in protein misfolding diseases. Semin. Cell Dev. Biol. 15, 17–29.10.1016/j.semcdb.2003.12.010Search in Google Scholar
Beere, H.M. (2004). “The stress of dying”: the role of heat shock proteins in the regulation of apoptosis. J. Cell Sci. 117, 2641–2651.10.1242/jcs.01284Search in Google Scholar
Bence, N.F., Sampat, R.M., and Kopito, R.R. (2001). Impairment of the ubiquitin-proteasome system by protein aggregation. Science 292, 1552–1555.10.1126/science.292.5521.1552Search in Google Scholar
Bennett, E.J., Shaler, T.A., Woodman, B., Ryu, K.Y., Zaitseva, T.S., Becker, C.H., Bates, G.P., Schulman, H., and Kopito, R.R. (2007). Global changes to the ubiquitin system in Huntington’s disease. Nature 448, 704–708.10.1038/nature06022Search in Google Scholar
Bentahir, M., Nyabi, O., Verhamme, J., Tolia, A., Horre, K., Wiltfang, J., Esselmann, H., and De Strooper, B. (2006). Presenilin clinical mutations can affect gamma-secretase activity by different mechanisms. J. Neurochem. 96, 732–742.10.1111/j.1471-4159.2005.03578.xSearch in Google Scholar
Bergeron, J.J., Brenner, M.B., Thomas, D.Y., and Williams, D.B. (1994). Calnexin: a membrane-bound chaperone of the endoplasmic reticulum. Trends Biochem. Sci. 19, 124–128.10.1016/0968-0004(94)90205-4Search in Google Scholar
Bonneau, R. and Baker, D. (2001). Ab initio protein structure prediction: progress and prospects. Annu. Rev. Biophys. Biomol. Struct. 30, 173–189.10.1146/annurev.biophys.30.1.173Search in Google Scholar PubMed
Brandvold, K.R. and Morimoto, R.I. (2015). The chemical biology of molecular chaperones–implications for modulation of proteostasis. J. Mol. Biol. 427, 2931–2947.10.1016/j.jmb.2015.05.010Search in Google Scholar PubMed PubMed Central
Brown, D.R., Qin, K., Herms, J.W., Madlung, A., Manson, J., Strome, R., Fraser, P.E., Kruck, T., von Bohlen, A., Schulz-Schaeffer, W., et al. (1997). The cellular prion protein binds copper in vivo. Nature 390, 684–687.10.1038/37783Search in Google Scholar PubMed
Bulawa, C.E., Connelly, S., DeVit, M., Wang, L., Weigel, C., Fleming, J.A., Packman, J., Powers, E.T., Wiseman, R.L., Foss, T.R., et al. (2012). Tafamidis, a potent and selective transthyretin kinetic stabilizer that inhibits the amyloid cascade. Proc. National Acad. Sci. 109, 9629–9634.10.1073/pnas.1121005109Search in Google Scholar PubMed PubMed Central
Bunn, H.F. (1997). Pathogenesis and treatment of sickle cell disease. N. Engl. J. Med. 337, 762–769.10.1056/NEJM199709113371107Search in Google Scholar PubMed
Calamini, B., Silva, M.C., Madoux, F., Hutt, D.M., Khanna, S., Chalfant, M.A., Saldanha, S.A., Hodder, P., Tait, B.D., Garza, D., et al. (2011). Small-molecule proteostasis regulators for protein conformational diseases. Nat. Chem. Biol. 8, 185–196.10.1038/nchembio.763Search in Google Scholar PubMed PubMed Central
Carbonell, F., Iturria-Medina, Y., and Evans, A.C. (2018). Mathematical modeling of protein misfolding mechanisms in neurological diseases: a historical overview. Front Neurol. 9, 37.10.3389/fneur.2018.00037Search in Google Scholar PubMed PubMed Central
Cardinale, A. and Biocca, S. (2013). Gene-based antibody strategies for prion diseases. Int. J. Cell Biol. 2013, 710406.10.1155/2013/710406Search in Google Scholar PubMed PubMed Central
Casadio, R., Compiani, M., Fariselli, P., Jacoboni, I., and Martelli, P.L. (2000). Neural networks predict protein folding and structure: artificial intelligence faces biomolecular complexity. SAR QSAR Environ. Res. 11, 149–182.10.1080/10629360008039120Search in Google Scholar PubMed
Chen, L., Leng, W.B., Li, Z., Xia, H.W., Ren, M., Tang, Q.L., Gong, Q.Y., Gao, F.B., and Bi, F. (2017). Noninvasive imaging of Ras activity by monomolecular biosensor based on split-luciferase complementary assay. Sci. Rep. 7, 9945.10.1038/s41598-017-08358-3Search in Google Scholar PubMed PubMed Central
Chiti, F. and Dobson, C.M. (2006). Protein misfolding, functional amyloid, and human disease. Annu. Rev. Biochem. 75, 333–366.10.1146/annurev.biochem.75.101304.123901Search in Google Scholar
Citron, M., Westaway, D., Xia, W., Carlson, G., Diehl, T., Levesque, G., Johnson-Wood, K., Lee, M., Seubert, P., Davis, A., et al. (1997). Mutant presenilins of Alzheimer’s disease increase production of 42-residue amyloid β-protein in both transfected cells and transgenic mice. Nat. Med. 3, 67–72.10.1038/nm0197-67Search in Google Scholar
Collinge, J., Whittington, M.A., Sidle, K.C., Smith, C.J., Palmer, M.S., Clarke, A.R., and Jefferys, J.G. (1994). Prion protein is necessary for normal synaptic function. Nature 370, 295–297.10.1038/370295a0Search in Google Scholar
Collins, S., McLean, C.A., and Masters, C.L. (2001). Gerstmann-Straussler-Scheinker syndrome, fatal familial insomnia, and kuru: a review of these less common human transmissible spongiform encephalopathies. J. Clin. Neurosci. 8, 387–397.10.1054/jocn.2001.0919Search in Google Scholar
Collins, S.J., Lawson, V.A., and Masters, C.L. (2004). Transmissible spongiform encephalopathies. Lancet 363, 51–61.10.1016/S0140-6736(03)15171-9Search in Google Scholar
Contestabile, A. (2011). The history of the cholinergic hypothesis. Behav. Brain Res. 221, 334–340.10.1016/j.bbr.2009.12.044Search in Google Scholar PubMed
Cuervo, A.M., Stefanis, L., Fredenburg, R., Lansbury, P.T., and Sulzer, D. (2004). Impaired degradation of mutant alpha-synuclein by chaperone-mediated autophagy. Science 305, 1292–1295.10.1126/science.1101738Search in Google Scholar PubMed
Cummings, J.L. (2003). Alzheimer’s disease: from molecular biology to neuropsychiatry. Semin. Clin. Neuropsychiatry 8, 31–36.10.1053/scnp.2003.50005Search in Google Scholar PubMed
De Baets, G., Van Durme, J., van der Kant, R., Schymkowitz, J., and Rousseau, F. (2015). Solubis: optimize your protein. Bioinformatics 31, 2580–2582.10.1093/bioinformatics/btv162Search in Google Scholar PubMed
De Maio, A. (1999). Heat shock proteins: facts, thoughts, and dreams. Shock 11, 1–12.10.1097/00024382-199901000-00001Search in Google Scholar PubMed
Deleault, N.R., Harris, B.T., Rees, J.R., and Supattapone, S. (2007). Formation of native prions from minimal components in vitro. Proc. Natl. Acad. Sci. USA 104, 9741–9746.10.1073/pnas.0702662104Search in Google Scholar
Dickey, C.A., Kamal, A., Lundgren, K., Klosak, N., Bailey, R.M., Dunmore, J., Ash, P., Shoraka, S., Zlatkovic, J., Eckman, C.B., et al. (2007). The high-affinity HSP90-CHIP complex recognizes and selectively degrades phosphorylated tau client proteins. J. Clin. Invest. 117, 648–658.10.1172/JCI29715Search in Google Scholar
Dobson, C.M. (2004). Principles of protein folding, misfolding and aggregation. Semin. Cell Dev. Biol. 15, 3–16.10.1016/j.semcdb.2003.12.008Search in Google Scholar
dos Santos, T.G. (2015). Protein Misfolding and Propagation in Neurodegenerative Diseases. Young Perspectives for Old Diseases (Bentham Science Publishers), pp. 103–118.10.2174/9781608059928115010008Search in Google Scholar
Duenas, A.M., Goold, R., and Giunti, P. (2006). Molecular pathogenesis of spinocerebellar ataxias. Brain 129, 1357–1370.10.1093/brain/awl081Search in Google Scholar
Dunn, A.Y., Melville, M.W., and Frydman, J. (2001). Review: cellular substrates of the eukaryotic chaperonin TRiC/CCT. J. Struct. Biol. 135, 176–184.10.1006/jsbi.2001.4380Search in Google Scholar
Dutta, D., Barr, V.A., Akpan, I., Mittelstadt, P.R., Singha, L.I., Samelson, L.E., and Ashwell, J.D. (2017). Recruitment of calcineurin to the TCR positively regulates T cell activation. Nat. Immunol. 18, 196–204.10.1038/ni.3640Search in Google Scholar
Ellis, R.J. (2001). Macromolecular crowding: an important but neglected aspect of the intracellular environment. Curr. Opin. Struct. Biol. 11, 114–119.10.1016/S0959-440X(00)00172-XSearch in Google Scholar
Evangelisti, E., Cascella, R., Becatti, M., Marrazza, G., Dobson, C.M., Chiti, F., Stefani, M., and Cecchi, C. (2016). Binding affinity of amyloid oligomers to cellular membranes is a generic indicator of cellular dysfunction in protein misfolding diseases. Sci. Rep. 6, 32721.10.1038/srep32721Search in Google Scholar PubMed PubMed Central
Finkbeiner, S. (2011). Huntington’s Disease. Cold Spring Harb Perspect Biol. 3, a007476.10.1101/cshperspect.a007476Search in Google Scholar PubMed PubMed Central
Galvan, A. and Wichmann, T. (2008). Pathophysiology of parkinsonism. Clin. Neurophysiol. 119, 1459–1474.10.1016/j.clinph.2008.03.017Search in Google Scholar PubMed PubMed Central
Geoghegan, J.C., Valdes, P.A., Orem, N.R., Deleault, N.R., Williamson, R.A., Harris, B.T., and Supattapone, S. (2007). Selective incorporation of polyanionic molecules into hamster prions. J Biol Chem. 282, 36341–36353.10.1074/jbc.M704447200Search in Google Scholar PubMed PubMed Central
Gibb, W.R. and Lees, A.J. (1988). The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson’s disease. J. Neurol. Neurosurg. Psychiatry 51, 745–752.10.1136/jnnp.51.6.745Search in Google Scholar PubMed PubMed Central
Glickman, M.H. and Ciechanover, A. (2002). The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction. Physiol. Rev. 82, 373–428.10.1152/physrev.00027.2001Search in Google Scholar PubMed
Gordon, P.H. (2013). Amyotrophic Lateral Sclerosis: an update for 2013 Clinical Features, Pathophysiology, Management and Therapeutic Trials. Aging Dis. 4, 295–310.10.14336/AD.2013.0400295Search in Google Scholar PubMed PubMed Central
Greenlee, J.J. and Greenlee, M.H. (2015). The transmissible spongiform encephalopathies of livestock. ILAR J. 56, 7–25.10.1093/ilar/ilv008Search in Google Scholar PubMed
Gu, Z., Nakamura, T., and Lipton, S.A. (2010). Redox reactions induced by nitrosative stress mediate protein misfolding and mitochondrial dysfunction in neurodegenerative diseases. Mol. Neurobiol. 41, 55–72.10.1007/s12035-010-8113-9Search in Google Scholar PubMed PubMed Central
Hardy, J. and Selkoe, D.J. (2002). The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science 297, 353–356.10.1126/science.1072994Search in Google Scholar PubMed
Hartl, F.U., Bracher, A., and Hayer-Hartl, M. (2011). Molecular chaperones in protein folding and proteostasis. Nature 475, 324–332.10.1038/nature10317Search in Google Scholar PubMed
Hasegawa, M. (2016). Molecular Mechanisms in the Pathogenesis of Alzheimer’s disease and tauopathies-prion-like seeded aggregation and phosphorylation. Biomolecules. 6, E24.10.3390/biom6020024Search in Google Scholar PubMed PubMed Central
Hekmatimoghaddam, S., Zare-Khormizi, M.R., and Pourrajab, F. (2016). Underlying mechanisms and chemical/biochemical therapeutic approaches to ameliorate protein misfolding neurodegenerative diseases. Biofactors 43, 737–759.10.1002/biof.1264Search in Google Scholar
Hetz, C. (2012). The unfolded protein response: controlling cell fate decisions under ER stress and beyond. Nat. Rev. Mol. Cell. Biol. 13, 89–102.10.1038/nrm3270Search in Google Scholar
Holley, L.H. and Karplus, M. (1989). Protein secondary structure prediction with a neural network. Proc. Natl. Acad. Sci. USA 86, 152–156.10.1073/pnas.86.1.152Search in Google Scholar
Iliff, J.J., Wang, M., Liao, Y., Plogg, B.A., Peng, W., Gundersen, G.A., Benveniste, H., Vates, G.E., Deane, R., Goldman, S.A., et al. (2012). A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β. Sci. Transl. Med. 4, 147ra111–147ra111.10.1126/scitranslmed.3003748Search in Google Scholar
Iqbal, K., Alonso Adel, C., Chen, S., Chohan, M.O., El-Akkad, E., Gong, C.X., Khatoon, S., Li, B., Liu, F., Rahman, A., et al. (2005). Tau pathology in Alzheimer disease and other tauopathies. Biochim. Biophys. Acta 1739, 198–210.10.1016/j.bbadis.2004.09.008Search in Google Scholar
Jackrel, M.E. and Shorter, J. (2017). Protein-remodeling factors as potential therapeutics for neurodegenerative disease. Front. Neurosci. 11, 99.10.3389/fnins.2017.00099Search in Google Scholar
Karbowski, M. and Neutzner, A. (2012). Neurodegeneration as a consequence of failed mitochondrial maintenance. Acta Neuropathol. 123, 157–171.10.1007/s00401-011-0921-0Search in Google Scholar
Kawahara, M., Ohtsuka, I., Yokoyama, S., Kato-Negishi, M., and Sadakane, Y. (2011). Membrane incorporation, channel formation, and disruption of calcium homeostasis by Alzheimer’s β-amyloid protein. Int. J. Alzheimers Dis. 2011, 304583.10.4061/2011/304583Search in Google Scholar
Kayed, R., Head, E., Thompson, J.L., McIntire, T.M., Milton, S.C., Cotman, C.W., and Glabe, C.G. (2003). Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis. Science 300, 486–489.10.1126/science.1079469Search in Google Scholar
Kiernan, M.C., Vucic, S., Cheah, B.C., Turner, M.R., Eisen, A., Hardiman, O., Burrell, J.R., and Zoing, M.C. (2011). Amyotrophic lateral sclerosis. Lancet 377, 942–955.10.1016/S0140-6736(10)61156-7Search in Google Scholar
Kim, W.S., Kagedal, K., and Halliday, G.M. (2014). Alpha-synuclein biology in Lewy body diseases. Alzheimers Res Ther. 6, 73.10.1186/s13195-014-0073-2Search in Google Scholar PubMed PubMed Central
Kostelidou, K., Matis, I., and Skretas, G. (2018). Microbial genetic screens for monitoring protein misfolding associated with neurodegeneration: tools for identifying disease-relevant genes and for screening synthetic and natural compound libraries for the discovery of potential therapeutics. Curr Pharm Des. 24, 2055–2075.10.2174/1381612824666180515143752Search in Google Scholar PubMed
Kovacs, G.G. and Budka, H. (2008). Prion diseases: from protein to cell pathology. Am. J. Pathol. 172, 555–565.10.2353/ajpath.2008.070442Search in Google Scholar PubMed PubMed Central
Kramer, G., Boehringer, D., Ban, N., and Bukau, B. (2009). The ribosome as a platform for co-translational processing, folding and targeting of newly synthesized proteins. Nat. Struct. Mol. Biol. 16, 589–597.10.1038/nsmb.1614Search in Google Scholar PubMed
Kumar, A., Singh, A., and Ekavali. (2015). A review on Alzheimer’s disease pathophysiology and its management: an update. Pharmacol Rep. 67, 195–203.10.1016/j.pharep.2014.09.004Search in Google Scholar PubMed
Labbadia, J. and Morimoto, R.I. (2013). Huntington’s disease: underlying molecular mechanisms and emerging concepts. Trends Biochem. Sci. 38, 378–385.10.1016/j.tibs.2013.05.003Search in Google Scholar PubMed PubMed Central
Landles, C. and Bates, G.P. (2004). Huntingtin and the molecular pathogenesis of Huntington’s disease. Fourth in molecular medicine review series. EMBO Rep. 5, 958–963.10.1038/sj.embor.7400250Search in Google Scholar PubMed PubMed Central
Lee, A.S. (2005). The ER chaperone and signaling regulator GRP78/BiP as a monitor of endoplasmic reticulum stress. Methods 35, 373–381.10.1016/j.ymeth.2004.10.010Search in Google Scholar PubMed
Lee, B.H., Lee, M.J., Park, S., Oh, D.C., Elsasser, S., Chen, P.C., Gartner, C., Dimova, N., Hanna, J., Gygi, S.P., et al. (2010). Enhancement of proteasome activity by a small-molecule inhibitor of USP14. Nature. 467, 179–184.10.1038/nature09299Search in Google Scholar PubMed PubMed Central
Lesage, S. and Brice, A. (2009). Parkinson’s disease: from monogenic forms to genetic susceptibility factors. Hum. Mol. Genet. 18, R48–59.10.1093/hmg/ddp012Search in Google Scholar PubMed
Maccioni, R.B., Farias, G., Morales, I., and Navarrete, L. (2010). The revitalized tau hypothesis on Alzheimer’s disease. Arch. Med. Res. 41, 226–231.10.1016/j.arcmed.2010.03.007Search in Google Scholar PubMed
Mahley, R.W., Weisgraber, K.H., and Huang, Y. (2006). Apolipoprotein E4: a causative factor and therapeutic target in neuropathology, including Alzheimer’s disease. Proc. Natl. Acad. Sci. USA 103, 5644–5651.10.1073/pnas.0600549103Search in Google Scholar
Mandelkow, E.M. and Mandelkow, E. (2012). Biochemistry and cell biology of tau protein in neurofibrillary degeneration. Cold Spring Harb Perspect Med. 2, a006247.10.1101/cshperspect.a006247Search in Google Scholar
Manto, M.U. (2005). The wide spectrum of spinocerebellar ataxias (SCAs). Cerebellum 4, 2–6.10.1080/14734220510007914Search in Google Scholar
Marti-Renom, M.A., Stuart, A.C., Fiser, A., Sanchez, R., Melo, F., and Sali, A. (2000). Comparative protein structure modeling of genes and genomes. Annu. Rev. Biophys. Biomol. Struct. 29, 291–325.10.1146/annurev.biophys.29.1.291Search in Google Scholar
Martinez-Vicente, M., Talloczy, Z., Kaushik, S., Massey, A.C., Mazzulli, J., Mosharov, E.V., Hodara, R., Fredenburg, R., Wu, D.C., et al. (2008). Dopamine-modified alpha-synuclein blocks chaperone-mediated autophagy. J. Clin. Invest. 118, 777–788.Search in Google Scholar
Matilla-Duenas, A. (2012). The ever expanding spinocerebellar ataxias. Editorial. Cerebellum 11, 821–827.10.1007/s12311-012-0376-4Search in Google Scholar
McCracken, A.A. and Brodsky, J.L. (2003). Evolving questions and paradigm shifts in endoplasmic-reticulum-associated degradation (ERAD). Bioessays 25, 868–877.10.1002/bies.10320Search in Google Scholar
Melville, M.W., McClellan, A.J., Meyer, A.S., Darveau, A., and Frydman, J. (2003). The Hsp70 and TRiC/CCT chaperone systems cooperate in vivo to assemble the von Hippel-Lindau tumor suppressor complex. Mol. Cell Biol. 23, 3141–3151.10.1128/MCB.23.9.3141-3151.2003Search in Google Scholar
Meusser, B., Hirsch, C., Jarosch, E., and Sommer, T. (2005). ERAD: the long road to destruction. Nat. Cell Biol. 7, 766–772.10.1038/ncb0805-766Search in Google Scholar
Michalak, M., Corbett, E.F., Mesaeli, N., Nakamura, K., and Opas, M. (1999). Calreticulin: one protein, one gene, many functions. Biochem. J. 344 Pt 2, 281–292.10.1042/bj3440281Search in Google Scholar
Mitchell, J.D. and Borasio, G.D. (2007). Amyotrophic lateral sclerosis. Lancet 369, 2031–2041.10.1016/S0140-6736(07)60944-1Search in Google Scholar
Mossuto, M.F. (2013). Disulfide bonding in neurodegenerative misfolding diseases. Int. J. Cell Biol. 2013, 318319.10.1155/2013/318319Search in Google Scholar PubMed PubMed Central
Narayan, P., Ehsani, S., and Lindquist, S. (2014). Combating neurodegenerative disease with chemical probes and model systems. Nat. Chem. Biol. 10, 911–920.10.1038/nchembio.1663Search in Google Scholar PubMed
Nikolaev, A., McLaughlin, T., O’Leary, D.D., and Tessier-Lavigne, M. (2009). APP binds DR6 to trigger axon pruning and neuron death via distinct caspases. Nature 457, 981–989.10.1038/nature07767Search in Google Scholar PubMed PubMed Central
Nistor, M., Don, M., Parekh, M., Sarsoza, F., Goodus, M., Lopez, G.E., Kawas, C., Leverenz, J., Doran, E., Lott, I.T., et al. (2007). Alpha- and beta-secretase activity as a function of age and β-amyloid in Down syndrome and normal brain. Neurobiol. Aging 28, 1493–1506.10.1016/j.neurobiolaging.2006.06.023Search in Google Scholar PubMed PubMed Central
Orr, H.T. (2012). Cell biology of spinocerebellar ataxia. J. Cell Biol. 197, 167–177.10.1083/jcb.201105092Search in Google Scholar PubMed PubMed Central
Padovani, A., Costanzi, C., Gilberti, N., and Borroni, B. (2006). Parkinson’s disease and dementia. Neurol Sci. 27 (Suppl 1), S40–43.10.1007/s10072-006-0546-6Search in Google Scholar PubMed
Pallares, I. and Ventura, S. (2016). Understanding and predicting protein misfolding and aggregation: Insights from proteomics. Proteomics 16, 2570–2581.10.1002/pmic.201500529Search in Google Scholar PubMed
Pasinelli, P. and Brown, R.H. (2006). Molecular biology of amyotrophic lateral sclerosis: insights from genetics. Nat. Rev. Neurosci. 7, 710–723.10.1038/nrn1971Search in Google Scholar PubMed
Penke, B., Bogar, F., and Fulop, L. (2016). Protein folding and misfolding, endoplasmic reticulum stress in neurodegenerative diseases: in trace of novel drug targets. Curr. Protein Pept. Sci. 17, 169–182.10.2174/1389203716666151102104653Search in Google Scholar PubMed
Querfurth, H.W. and LaFerla, F.M. (2010). Alzheimer’s disease. N. Engl. J. Med. 362, 329–344.10.1056/NEJMra0909142Search in Google Scholar PubMed
Raber, J., Huang, Y., and Ashford, J.W. (2004). ApoE genotype accounts for the vast majority of AD risk and AD pathology. Neurobiol. Aging 25, 641–650.10.1016/j.neurobiolaging.2003.12.023Search in Google Scholar
Rawlins, M.D., Wexler, N.S., Wexler, A.R., Tabrizi, S.J., Douglas, I., Evans, S.J., and Smeeth, L. (2016). The prevalence of Huntington’s disease. Neuroepidemiology 46, 144–153.10.1159/000443738Search in Google Scholar
Rochet, J.C. and Lansbury, P.T., Jr. (2000). Amyloid fibrillogenesis: themes and variations. Curr. Opin. Struct. Biol. 10, 60–68.10.1016/S0959-440X(99)00049-4Search in Google Scholar
Ross, C.A. and Poirier, M.A. (2004). Protein aggregation and neurodegenerative disease. Nat. Med. 10 (Suppl), S10–S17.10.1038/nm1066Search in Google Scholar PubMed
Safar, J.G., Kellings, K., Serban, A., Groth, D., Cleaver, J.E., Prusiner, S.B., and Riesner, D. (2005). Search for a prion-specific nucleic acid. J. Virol. 79, 10796–10806.10.1128/JVI.79.16.10796-10806.2005Search in Google Scholar PubMed PubMed Central
Saibil, H. (2013). Chaperone machines for protein folding, unfolding and disaggregation. Nat. Rev. Cancer 13, 630–642.10.1038/nrm3658Search in Google Scholar PubMed PubMed Central
Sali, A. (1995). Comparative protein modeling by satisfaction of spatial restraints. Mol. Med. Today 1, 270–277.10.1107/S0108767396095578Search in Google Scholar
Sant’Anna, R., Gallego, P., Robinson, L.Z., Pereira-Henriques, A., Ferreira, N., Pinheiro, F., Esperante, S., Pallares, I., Huertas, O., Rosário Almeida, M., et al. (2016). Repositioning tolcapone as a potent inhibitor of transthyretin amyloidogenesis and associated cellular toxicity. Nat Commun. 7, 10787.10.1038/ncomms10787Search in Google Scholar PubMed PubMed Central
Scannevin, R.H. (2018). Therapeutic strategies for targeting neurodegenerative protein misfolding disorders. Curr. Opin. Chem. Biol. 44, 66–74.10.1016/j.cbpa.2018.05.018Search in Google Scholar PubMed
Schapira, A.H. (1999). Science, medicine, and the future: Parkinson’s disease. Br. Med. J. 318, 311–314.10.1136/bmj.318.7179.311Search in Google Scholar PubMed PubMed Central
Schmitz, M., Cramm, M., Llorens, F., Muller-Cramm, D., Collins, S., Atarashi, R., Satoh, K., Orru, C.D., Groveman, B.R., Zafar, S., et al. (2016). The real-time quaking-induced conversion assay for detection of human prion disease and study of other protein misfolding diseases. Nat. Protoc. 11, 2233–2242.10.1038/nprot.2016.120Search in Google Scholar PubMed
Shah, S.Z., Hussain, T., Zhao, D., and Yang, L. (2017). A central role for calcineurin in protein misfolding neurodegenerative diseases. Cell Mol Life Sci. 74, 1061–1074.10.1007/s00018-016-2379-7Search in Google Scholar PubMed
Sheahan, A.V., Sekar, T.V., Chen, K., Paulmurugan, R., and Massoud, T.F. (2016). A molecular imaging biosensor detects in vivo protein folding and misfolding. J. Mol. Med. (Berl). 94, 799–808.10.1007/s00109-016-1437-9Search in Google Scholar PubMed
Shulman, J.M., De Jager, P.L., and Feany, M.B. (2011). Parkinson’s disease: genetics and pathogenesis. Annu. Rev. Pathol. 6, 193–222.10.1146/annurev-pathol-011110-130242Search in Google Scholar PubMed
Singleton, A.B., Farrer, M., Johnson, J., Singleton, A., Hague, S., Kachergus, J., Hulihan, M., Peuralinna, T., Dutra, A., Nussbaum, R., et al. (2003). alpha-Synuclein locus triplication causes Parkinson’s disease. Science 302, 841.10.1126/science.1090278Search in Google Scholar PubMed
Sittler, A., Lurz, R., Lueder, G., Priller, J., Lehrach, H., Hayer-Hartl, M.K., Hartl, F.U., and Wanker, E.E. (2001). Geldanamycin activates a heat shock response and inhibits huntingtin aggregation in a cell culture model of Huntington’s disease. Hum. Mol. Genet. 10, 1307–1315.10.1093/hmg/10.12.1307Search in Google Scholar PubMed
Solomon, I.H., Biasini, E., and Harris, D.A. (2012). Ion channels induced by the prion protein: mediators of neurotoxicity. Prion 6, 40–45.10.4161/pri.6.1.18627Search in Google Scholar PubMed PubMed Central
Sormanni, P., Aprile, F.A., and Vendruscolo, M. (2015). The CamSol method of rational design of protein mutants with enhanced solubility. J. Mol. Biol. 427, 478–490.10.1016/j.jmb.2014.09.026Search in Google Scholar PubMed
Soto, C. (2003). Unfolding the role of protein misfolding in neurodegenerative diseases. Nat. Rev. Neurosci. 4, 49–60.10.1038/nrn1007Search in Google Scholar PubMed
Soto, C. (2011). Prion hypothesis: the end of the controversy? Trends Biochem. Sci. 36, 151–158.Search in Google Scholar
Soto, C. and Castilla, J. (2004). The controversial protein-only hypothesis of prion propagation. Nat. Med. 10 (Suppl), S63–67.10.1038/nm1069Search in Google Scholar PubMed
Soto, C., Estrada, L., and Castilla, J. (2006). Amyloids, prions and the inherent infectious nature of misfolded protein aggregates. Trends Biochem. Sci. 31, 150–155.10.1016/j.tibs.2006.01.002Search in Google Scholar PubMed
Spillantini, M.G., Crowther, R.A., Jakes, R., Hasegawa, M., and Goedert, M. (1998). alpha-Synuclein in filamentous inclusions of Lewy bodies from Parkinson’s disease and dementia with lewy bodies. Proc. Natl. Acad. Sci. USA 95, 6469–6473.10.1073/pnas.95.11.6469Search in Google Scholar PubMed PubMed Central
Spillantini, M.G., Schmidt, M.L., Lee, V.M., Trojanowski, J.Q., Jakes, R., and Goedert, M. (1997). Alpha-synuclein in Lewy bodies. Nature 388, 839–840.10.1038/42166Search in Google Scholar PubMed
Sulzer, D. (2010). Clues to how alpha-synuclein damages neurons in Parkinson’s disease. Mov. Disord. 25 (Suppl 1), S27–31.10.1002/mds.22639Search in Google Scholar PubMed
Supattapone, S. (2010). Biochemistry. What makes a prion infectious? Science 327, 1091–1092.Search in Google Scholar
Thies, W., Bleiler, L., and Alzheimer’s, A. (2013). 2013 Alzheimer’s disease facts and figures. Alzheimers Dement. 9, 208–245.10.1016/j.jalz.2013.02.003Search in Google Scholar PubMed
Tsigelny, I.F., Sharikov, Y., Wrasidlo, W., Gonzalez, T., Desplats, P.A., Crews, L., Spencer, B., and Masliah, E. (2012). Role of α-synuclein penetration into the membrane in the mechanisms of oligomer pore formation. FEBS J. 279, 1000–1013.10.1111/j.1742-4658.2012.08489.xSearch in Google Scholar PubMed PubMed Central
Turner, M.R., Bowser, R., Bruijn, L., Dupuis, L., Ludolph, A., McGrath, M., Manfredi, G., Maragakis, N., Miller, R.G., Pullman, S.L., et al. (2013). Mechanisms, models and biomarkers in amyotrophic lateral sclerosis. Amyotroph. Lateral Scler. Frontotemporal Degener. 14 (Suppl 1), 19–32.10.3109/21678421.2013.778554Search in Google Scholar PubMed PubMed Central
Ugalde, C.L., Finkelstein, D.I., Lawson, V.A., and Hill, A.F. (2016). Pathogenic mechanisms of prion protein, amyloid-beta and alpha-synuclein misfolding: the prion concept and neurotoxicity of protein oligomers. J. Neurochem. 139, 162–180.10.1111/jnc.13772Search in Google Scholar PubMed
Walker, F.O. (2007). Huntington’s disease. Semin. Neurol. 27, 143–150.10.1055/s-2007-971176Search in Google Scholar PubMed
Wang, F., Wang, X., Yuan, C.G., and Ma, J. (2010). Generating a prion with bacterially expressed recombinant prion protein. Science 327, 1132–1135.10.1126/science.1183748Search in Google Scholar PubMed PubMed Central
Weissmann, C., Enari, M., Klohn, P.C., Rossi, D., and Flechsig, E. (2002). Transmission of prions. J. Infect. Dis. 186 (Suppl 2), S157–165.10.1086/344575Search in Google Scholar
Weller, R.O., Subash, M., Preston, S.D., Mazanti, I., and Carare, R.O. (2008). Perivascular drainage of amyloid-beta peptides from the brain and its failure in cerebral amyloid angiopathy and Alzheimer’s disease. Brain Pathol. 18, 253–266.10.1111/j.1750-3639.2008.00133.xSearch in Google Scholar
Wenk, G.L. (2003). Neuropathologic changes in Alzheimer’s disease. J. Clin. Psychiatry 64 (Suppl 9), 7–10.Search in Google Scholar
Wilkinson, B. and Gilbert, H.F. (2004). Protein disulfide isomerase. Biochim Biophys Acta 1699, 35–44.10.1016/S1570-9639(04)00063-9Search in Google Scholar
Yoshida, Y. (2003). A novel role for N-glycans in the ERAD system. J Biochem. 134, 183–190.10.1093/jb/mvg128Search in Google Scholar PubMed
Zambrano, R., Jamroz, M., Szczasiuk, A., Pujols, J., Kmiecik, S., and Ventura, S. (2015). AGGRESCAN3D (A3D): server for prediction of aggregation properties of protein structures. Nucleic Acids Res. 43, W306–W313.10.1093/nar/gkv359Search in Google Scholar PubMed PubMed Central
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