Neurotoxicity Research

, Volume 23, Issue 1, pp 69–78 | Cite as

Reciprocal Induction Between α-Synuclein and β-Amyloid in Adult Rat Neurons

  • Shohreh MajdEmail author
  • Fariba Chegini
  • Tim Chataway
  • Xin-Fu Zhou
  • Weiping Gai
Original Article


In spite of definite roles for β-amyloid (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 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 Aβ 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 Aβ1-42 or α-Syn on mature neurons and the effects of Aβ1-42 or α-Syn on the production of endogenous α-Syn or Aβ1-40 reciprocally using a model of culture enriched with primary neurons from the hippocampus of adult rats. Treatment of neurons with high concentrations of Aβ1-42 or α-Syn caused significant apoptosis of neurons. Following Aβ1-42 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 Aβ1-40 levels. The phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002, suppressed α-Syn-induced Aβ1-40 elevation, as well as Aβ1-42-induced α-Syn elevation. Thus, high concentrations of Aβ1-42 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.


β-Amyloid α-Synuclein Adult neurons Neuronal death Alzheimer’s disease Parkinson’s disease Phosphatidylinositol 3-kinase (PI3K) 



This study was supported by NHMRC grants to Xin-Fu Zhou (595937) and Weiping Gai (535014).


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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Shohreh Majd
    • 1
    Email author
  • Fariba Chegini
    • 1
  • Tim Chataway
    • 1
  • Xin-Fu Zhou
    • 1
  • Weiping Gai
    • 1
  1. 1.Department of Human Physiology and Centre for NeuroscienceFlinders UniversityAdelaideAustralia

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