A calcineurin and NFAT-dependent pathway is involved in asynuclein-induced degeneration of midbrain dopaminergic neurons
作者单位：北京师范大学
会议名称：《中国生物化学与分子生物学会第十一次会员代表大会暨201...》
会议日期：2014年
学科分类：0710[理学-生物学] 07[理学] 071006[理学-神经生物学]
关 键 词：Parkinson Disease calcineurin alpha synuclein NFAT midbrain A53T transgenic mice
摘 要：Parkinson’s disease(PD),the most common degenerative movement disorder,is causedby a preferential loss of midbrain dopaminergic(mDA)*** a-synuclein(a-syn)missense and multiplication mutations have been linked to ***,the underlyingintracellular signalling transduction pathways of a-syn-mediated mDA neurodegenerationremain ***,we show that transgenic expression of PD-related human a-syn A53Tmissense mutation promoted calcineurin(CN)activity and the subsequent nuclear translocationof nuclear factor of activated T-cells(NFAT)in mDA neurons.a-syn enhanced thephosphatase activity of CN in both cell-free assays and cell lines transfected with either humanwild-type or A53T ***,over-expression of a-syn A53T mutation significantlyincreased the CN-dependent nuclear import of NFATc3 in the mDA neurons oftransgenic *** importantly,a pharmacological inhibition of CN by cyclosporine A(CsA)ameliorated the a-syn-induced loss of mDA *** findings demonstrate theactive involvement of the CNand NFAT-mediated signalling pathway in the a-synmediateddegeneration of mDA neurons in PD.