摘要亨廷顿病是一种单基因常染色体显性遗传性神经退行性疾病,以脑内纹状体神经元大量丢失为主要病理特征,临床表现为不自主的舞蹈样运动、认知障碍和神经精神症状.其发病机制主要是突变亨廷顿蛋白的表达,导致纹状体中中型多棘神经元的选择性变性和疾病的发作.大麻素受体(cannabinoid receptor,CBR)主要通过CBR1和CBR2信号途径在神经递质释放、突触可塑性、基因表达和神经元活性的调制等方面发挥关键作用.近年来研究发现,CBR1介导的磷脂酰肌醇3-激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白复合物1/脑源性神经营养因子、神经肽Y/神经元一氧化氮合酶等相关信号通路在调节亨廷顿病纹状体神经保护中发挥关键作用.我们着重综述有关CBR1相关信号通路在亨廷顿病中作用的研究进展,为防治亨廷顿病提供新的理论依据和药物靶点.

abstractsHuntington's disease (HD),a single-gene autosomal dominant neurodegenerative disease,is pathologically characterized by the great loss of striatal neurons in the brain.Clinical manifestations of HD show involuntary dance-like movements,cognitive function and neuropsychiatric symptoms.The pathogenesis of HD is concerned with the protein expression of mutant huntingtin which leads to the selective degeneration of medium spiny neurons in the striatum and the onset of the disease.Cannabinoid receptor (CBR) plays a key role in the release of neurotransmitters,synaptic plasticity,gene expression and modulation of.neuronal activity through the CBR1 and CBR2 signaling pathways.Recent studies have found that CBR-mediated phosphoinositide3-kinases/protein kinase B/mammalian target of rapamycin complex1/brain derived neurotrophic factor,neuropeptide Y/neuronal nitric oxide synthase signaling pathway play a vital role in the regulation.of striatal neuroprotection in HD.This review reveals the research progress of CBR1 related signaling pathways in HD,which provides new theoretical basis and drug targets for the prevention and treatment of HD.