Linking alpha-synuclein properties with oxidation: a hypothesis on a mechanism underling cellular aggregation
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α-Synuclein is a small, natively unstructured protein with propensity to aggregate. α-Synuclein fibrils are major components of Lewy bodies that are hallmarks of many neurodegenerative diseases. The solution properties and aggregation behavior of α-synuclein has been well characterized, but despite numerous studies that address the role of α-synuclein in cells, a clear physiological function of this protein remains a mystery. Over a hundred review articles of α-synuclein have been written in the last decade, making it difficult to list all of the important studies that have added to our insight of α-synuclein physiology. Instead, we briefly review the status of α-synuclein research and propose a model based on the idea that α-synuclein may not have an intrinsic activity in cells but rather, it modifies the function of a group of protein partners that in turn affect cell processes. We propose that it is the loss of its cellular partners under oxidative conditions that promotes α-synuclein aggregation accelerating neuronal death.
Keywordsα-Synuclein Protein aggregation Oxidative stress Phospholipase C
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- Bartels T, Choi JG, Selkoe DJ (2011) [agr]-Synuclein occurs physiologically as a helically folded tetramer that resists aggregation. Nature 477(7362):107–110. doi: 10.1038/nature10324, http://www.nature.com/nature/journal/v477/n7362/abs/nature10324.html#supplementary-information CrossRefGoogle Scholar
- George JM (2002) The synucleins. Genome Biol 3:3002.3001–3002.3006Google Scholar
- Murphy DD, Rueter SM, Trojanowski JQ, Lee VM (2000) Synucleins are developmentally expressed, and alpha-synuclein regulates the size of the presynaptic vesicular pool in primary hippocampal neurons. J Neurosci 20(9):3214–3220Google Scholar
- Ostrerova N, Petrucelli L, Farrer M, Mehta N, Choi P, Hardy J et al (1999) a-Synuclein shares physical and functional homology with 14-3-3 proteins. J Neurosci 19(14):5782–5791Google Scholar
- Rebecchi MJ, Pentyala SN (2000) Structure, function, and control of phosphoinositide-specific phospholipase C. Physiol Rev 80:1291–1335Google Scholar
- Zhou W, Hurlbert MS, Schaack J, Prasad KN, Freed CR (2000) Overexpression of human alpha-synuclein causes dopamine neuron death in rat primary culture and immortalized mesencephalon-derived cells. Brain Res 866(1–2):33–43Google Scholar