共 54 条
Reciprocal Induction Between α-Synuclein and β-Amyloid in Adult Rat Neurons
被引:18
作者:
Majd, Shohreh
[1
,2
]
Chegini, Fariba
[1
,2
]
Chataway, Tim
[1
,2
]
Zhou, Xin-Fu
[1
,2
]
Gai, Weiping
[1
,2
]
机构:
[1] Flinders Univ S Australia, Dept Human Physiol, Adelaide, SA 5001, Australia
[2] Flinders Univ S Australia, Ctr Neurosci, Adelaide, SA 5001, Australia
基金:
英国医学研究理事会;
澳大利亚国家健康与医学研究理事会;
关键词:
beta-Amyloid;
alpha-Synuclein;
Adult neurons;
Neuronal death;
Alzheimer's disease;
Parkinson's disease;
Phosphatidylinositol 3-kinase (PI3K);
ALZHEIMERS-DISEASE;
PRECURSOR PROTEIN;
A-BETA;
NEUROBLASTOMA-CELLS;
RISK-FACTORS;
BRAIN;
EXPRESSION;
AGGREGATION;
SECRETASE;
INVOLVEMENT;
D O I:
10.1007/s12640-012-9330-y
中图分类号:
Q189 [神经科学];
学科分类号:
071006 ;
摘要:
In spite of definite roles for beta-amyloid (A beta) 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 A beta and alpha-synuclein (alpha-Syn), the principle components in the pathological structures, in neuronal toxicity and the mechanisms of their interaction are not well studied. As A beta and alpha-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 A beta 1-42 or alpha-Syn on mature neurons and the effects of A beta 1-42 or alpha-Syn on the production of endogenous alpha-Syn or A beta 1-40 reciprocally using a model of culture enriched with primary neurons from the hippocampus of adult rats. Treatment of neurons with high concentrations of A beta 1-42 or alpha-Syn caused significant apoptosis of neurons. Following A beta 1-42 treatment at sub apoptotic concentrations, both intra- and extra-cellular alpha-Syn levels were significantly increased. Reciprocally, the non-toxic levels of alpha-Syn treatment also increased intra- and extra-cellular A beta 1-40 levels. The phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002, suppressed alpha-Syn-induced A beta 1-40 elevation, as well as A beta 1-42-induced alpha-Syn elevation. Thus, high concentrations of A beta 1-42 and alpha-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.
引用
收藏
页码:69 / 78
页数:10
相关论文