α-Synuclein oligomers oppose long-term potentiation and impair memory through a calcineurin-dependent mechanism: relevance to human synucleopathic diseases.

ABSTRACT: Intracellular deposition of fibrillar aggregates of α-synuclein (αSyn) characterizes neurodegenerative diseases such as Parkinson's disease (PD) and dementia with Lewy bodies. However, recent evidence indicates that small αSyn oligomeric aggregates that precede fibril formation may be the most neurotoxic species and can be found extracellularly. This new evidence has changed the view of pathological αSyn aggregation from a self-contained cellular phenomenon to an extracellular event and prompted investigation of the putative effects of extracellular αSyn oligomers. In this study, we report that extracellular application of αSyn oligomers detrimentally impacts neuronal welfare and memory function. We found that oligomeric αSyn increased intracellular Ca(2+) levels, induced calcineurin (CaN)

SUBMITTER: Martin ZS 

PROVIDER: S-EPMC3253169 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature