Alpha-synuclein aggregation

Narhi L, Wood SJ, Steavenson S, Jiang Y, Wu GM, Anafi D, Kaufman SA, Martin F, Sitney K, Denis P, Louis JC, Wypych J, Biere AL, Citron M. Both familial Parkinson s disease mutations accelerate alpha-synuclein aggregation. J Biol Chem 1999 274 9843-9846. 

Lee SJ. Alpha-synuclein aggregation a link between mitochondrial defects and Parkinson s disease Antioxid Redox Signal. 2003 5 337-348. 

C., Madsen, P., Nyengaard, J. R., Ho-jrup, P., Moos, T., Otzen, D., Gai, W. P., Blumbergs, P. C., Jensen, P. H. p25alpha stimulates alpha-synuclein aggregation and is co-localized with aggregated alpha-synuclein in alpha-synucleinopathies. J. Biol. Chem. 2005, 280 5703-5715. 

One might speculate that seeds arise from mutant forms of protein. For some of the discussed diseases this could be proven in cell culture models. Proteins like Huntingtin, amyloid-P and alpha-synuclein aggregate in vitro and in transfected COS cells. Models of SCA-3 show nuclear inclusions with wildtype and mutated protein [14]. Another example for this situation is found in AD plaques, where a peptide with a partial alpha-synuclein sequences seeds P-amyloid polymerization in vitro [32]. 

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Qiao L, Hamamichi S, Caldwell K et al. (2008) Lysosomal enzyme cathepsin D protects against alpha-synuclein aggregation and toxicity. Mol Brain 1, 17. 

Pacheco C, Aguayo LG, Opazo C. An extracellular mechanism that can explain the neurotoxic effects of alpha-synuclein aggregates in the brain. Front Physiol. 2012 3 297. 

Lee HJ, Suk JE, Bae EJ, Lee SJ. aearance and deposition of extracellular alpha-synuclein aggregates in microglia. Biochem Biophys Res Commun. 2008 372(3) 423-428. 

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Lashuel, H. A., Petre, B. M., Wall, J., Simon, M., Nowak, R. J., Walz, T., and Lansbury, P. T., Jr. (2002). Alpha-synuclein, especially the Parkinson s disease-associated mutants, forms pore-like annular and tubular protofibrils./. Mol. Biol. 322,1089-1102. LeVine, H. (1993). Thioflavine T interaction with synthetic Alzheimer s disease beta-amyloid peptides Detection of amyloid aggregation in solution. Protein Sci. 2, 404—410. Lin, H., Bhatia, R., and Lai, R. (2001). Amyloid beta protein forms ion channels Implications for Alzheimer s disease pathophysiology. FASEB J. 15, 2433-2444. Lorenzo, A., and Yankner, B. A. (1994). Beta-amyloid neurotoxicity requires fibril formation and is inhibited by Congo red. Proc. Natl. Acad. Sci. USA 91, 12243-12247. Luhrs, T., Ritter, C., Adrian, M., Riek-Loher, D., Bohrmann, B., Dobeli, H., Schubert, D., and Riek, R. (2005). 3D structure of Alzheimer s amyl o id-( be la) (1—12) fibrils. Proc. Natl. Acad. Sci. USA 102, 17342-17347. 

Junn, E., Ronchetti, R. D., Quezado, M. M., Kim, S. Y., and Mouradian, M. M. (2003). Tissue transglutaminase-induced aggregation of alpha-synuclein Implications for Lewy body formation in Parkinson s disease and dementia with Lewy bodies. Proc. Natl. Acad. Sci. USA 100, 2047-2052. 

El-Agnaf OM, Jakes R, Curran MD, Middleton D, Ingenito R, BiancM E, Pessi A, NeUl D, WaUace A (1998) Aggregates from mutant and wUd-type alpha-synuclein proteins and NAC peptide induce apoptotic ceU death in human neuroblastoma ceUs by formation of beta-sheet and amyloid-hke filaments. FEBS Lett 440 71-75 Esler WP, Wolfe MS (2001) A portrait of Alzheimer secretases - new features and familiar faces. Science 293 1449-1454... 

Pals P, Lincoln S, Manning J, Heckman M, Skipper L, Hulihan M, Van den BroeckM, De Footer T, Cras P, Crook J, Van Broeckhoven C, Farrer Ml (2004) tilpha-Synuclein promoter confers susceptibility to Parkinson s disease. Ann Neurol 56 591-595 Pandey N, Schmidt RE, Galvin JE (2006) The alpha-synuclein mutation E46K promotes aggregation in cultured cells. Exp Neurol 197 515-520... 

LeeHJ, Patel S, Lee SJ (2005) Intravesicular localization and exocytosis of alpha-synuclein and its aggregates. J Neurosd 25 6016-6024. 

Emadi S, Liu R, Yuan B, Schulz P, McAllister C, Lyubchenko Y, Messer A, Sierks MR (2004) Inhibiting aggregation of alpha-synuclein with human single chain antibody fragments. Biochemistry 43 2871-2878. 

Emadi S, Barkhordarian H, Wang MS, Schulz P, Sierks MR (2007) Isolation of a human single chain antibody fragment against oligomeric alpha-synuclein that inhibits aggregation and prevents alpha-synuclein-induced toxicity. J Mol Biol 368 1132-1144. 

Drescher M, van Rooijen BD, Veldhuis G, Subramaniam V, Huber M (2010) A stable lipid-induced aggregate of alpha-synuclein. J Am Chem Soc 132 4080-4081... 

Hashimoto, M., L. J. Hsu, Y. Xia et al. Oxidative stress induces amyloid-like aggregate formation of NACP/alpha-synuclein in vitro. 10(4), 1999 717-21. 

Jakobsen L.D., Jensen P.H. (2003) Parkinson s disease alpha-synuclein and parkin in protein aggregation and the reversal of unfolded protein stress. Methods Mol Biol, 232 57-66. 

Bertoncini CW, Jung YS, Fernandez CO, et al. Release of long-range tertiary interactions potentiates aggregation of natively unstructured alpha-synuclein. Proc Natl Acad Sci USA. 2005 1Q2(5) 1430-1435. 

Bartels T, Kim NC, Luth ES, Selkoe DJ. N-alpha-acetylation of alpha-synuclein increases its helical folding propensity, GMl binding specificity and resistance to aggregation. PloS One. 2014 9(7) el03727. 

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