Reciprocal induction between α-synuclein and ß-amyloid in adult rat neurons.

In spite of definite roles for ß-amyloid (Aß) in familial Alzheimer's disease (AD), the cause of sporadic AD remains unknown. Amyloid senile plaques and Lewy body pathology frequently coexist in neocortical and hippocampal regions of AD and Parkinson's diseases. However, the relationship between Aß and α-synuclein (α-Syn), the principle components in the pathological structures, in neuronal toxicity and the mechanisms of their interaction are not well studied. As Aß and α-Syn accumulate in aging patients, the biological functions and toxicity of these polypeptides in the aging brain may be different from those in young brain. We examined the neurotoxicity influences of Aß1-42 or α-Syn on mature neurons and the effects of Aß1-42 or α-Syn on the production of endogenous α-Syn or Aß1-40 reciprocally using a model of culture enriched with primary neurons from the hippocampus of adult rats. Treatment of neurons with high concentrations of Aß1-42 or α-Syn caused significant apoptosis of neurons. Following Aß1-42 treatment at sub apoptotic concentrations, both intra- and extra-cellular α-Syn levels were significantly increased. Reciprocally, the non-toxic levels of α-Syn treatment also increased intra- and extra-cellular Aß1-40 levels. The phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002, suppressed α-Syn-induced Aß1-40 elevation, as well as Aß1-42-induced α-Syn elevation. Thus, high concentrations of Aß1-42 and α-Syn exert toxic effects on mature neurons; however, non-toxic concentration treatment of these polypeptides induced the production of each other reciprocally with possible involvement of PI3K pathway.