Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Robert-Rössle-Straße 10, 13125 Berlin, Germany.
Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Robert-Rössle-Straße 10, 13125 Berlin, Germany; Freie Universität Berlin, Faculty of Biology, Chemistry, Pharmacy, 14195 Berlin, Germany.
Curr Opin Neurobiol. 2018 Feb;48:153-159. doi: 10.1016/j.conb.2017.12.018. Epub 2018 Jan 6.
Neuronal signaling depends on the exocytic fusion and subsequent endocytic retrieval and reformation of neurotransmitter-containing synaptic vesicles at synapses. Recent findings have uncovered surprising roles of presynaptic endocytic proteins in the formation and transport of autophagosomes. These include functions of the membrane remodelling protein endophilin and its downstream effector, the phosphoinositide phosphatase synaptojanin, in autophagosome formation and in Parkinson's disease, the endocytic sorting adaptor CALM in protein degradation via the autophagy/lysosomal pathway in Alzheimer's disease, and the clathrin adaptor complex AP-2 in retrograde transport of signaling autophagosomes to prevent neurodegeneration. These findings reveal unanticipated connections between the machineries for synaptic neurotransmission and neuronal proteostasis and identify presynaptic endocytic proteins as potential targets to treat neurodegenerative diseases.
神经元信号依赖于突触处含神经递质的突触小泡的出胞融合，以及随后的内吞回收和再形成。最近的研究结果揭示了突触前内吞蛋白在自噬体形成和运输中的惊人作用。这些作用包括膜重塑蛋白神经末梢蛋白（endophilin）及其下游效应物磷酸肌醇磷酸酶（synaptojanin）在自噬体形成和帕金森病中的作用，内吞分选衔接蛋白（CALM）在阿尔茨海默病中通过自噬/溶酶体途径进行蛋白降解的作用，以及网格蛋白衔接蛋白复合物（AP-2）在信号自噬体逆行运输中的作用，以防止神经退行性病变。这些发现揭示了突触神经传递和神经元蛋白稳态之间出人意料的联系，并将突触前内吞蛋白确定为治疗神经退行性疾病的潜在靶点。
