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Neurotox Res. 2009 Oct;16(3):306-17. doi: 10.1007/s12640-009-9073-6. Epub 2009 Jun 24.

Role of synucleins in Alzheimer's disease.

Author information

1
Department of Neurosciences, University of California San Diego, La Jolla, CA 92093-0624, USA.

Abstract

Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common causes of dementia and movement disorders in the elderly. While progressive accumulation of oligomeric amyloid-beta protein (Abeta) has been identified as one of the central toxic events in AD leading to synaptic dysfunction, accumulation of alpha-synuclein (alpha-syn) resulting in the formation of oligomers has been linked to PD. Most of the studies in AD have been focused on investigating the role of Abeta and Tau; however, recent studies suggest that alpha-syn might also play a role in the pathogenesis of AD. For example, fragments of alpha-syn can associate with amyloid plaques and Abeta promotes the aggregation of alpha-syn in vivo and worsens the deficits in alpha-syn tg mice. Moreover, alpha-syn has also been shown to accumulate in limbic regions in AD, Down's syndrome, and familial AD cases. Abeta and alpha-syn might directly interact under pathological conditions leading to the formation of toxic oligomers and nanopores that increase intracellular calcium. The interactions between Abeta and alpha-syn might also result in oxidative stress, lysosomal leakage, and mitochondrial dysfunction. Thus, better understanding the steps involved in the process of Abeta and alpha-syn aggregation is important in order to develop intervention strategies that might prevent or reverse the accumulation of toxic proteins in AD.

PMID:
19551456
PMCID:
PMC2727399
DOI:
10.1007/s12640-009-9073-6
[Indexed for MEDLINE]
Free PMC Article

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