Reciprocal Induction Between αSynuclein and βAmy

Authors: Shohreh Majd Fariba Chegini Tim Chataway XinFu Zhou Weiping Gai

Publish Date: 2012/05/19

Volume: 23, Issue: 1, Pages: 69-78

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Abstract

In spite of definite roles for βamyloid Aβ 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 Aβ and αsynuclein αSyn the principle components in the pathological structures in neuronal toxicity and the mechanisms of their interaction are not well studied As Aβ and αSyn 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 Aβ142 or αSyn on mature neurons and the effects of Aβ142 or αSyn on the production of endogenous αSyn or Aβ140 reciprocally using a model of culture enriched with primary neurons from the hippocampus of adult rats Treatment of neurons with high concentrations of Aβ142 or αSyn caused significant apoptosis of neurons Following Aβ142 treatment at sub apoptotic concentrations both intra and extracellular αSyn levels were significantly increased Reciprocally the nontoxic levels of αSyn treatment also increased intra and extracellular Aβ140 levels The phosphatidylinositol 3kinase PI3K inhibitor LY294002 suppressed αSyninduced Aβ140 elevation as well as Aβ142induced αSyn elevation Thus high concentrations of Aβ142 and αSyn exert toxic effects on mature neurons however nontoxic concentration treatment of these polypeptides induced the production of each other reciprocally with possible involvement of PI3K pathway

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