Myers Abigail J, Brahimi Ayat, Jenkins Imani J, Koob Andrew O
Neuroscience Program, Health Science Research Facility, University of Vermont, 149 Beaumont Ave., Burlington, VT 05405, USA.
Biology Department, University of Hartford, 200 Bloomfield Ave., West Hartford, CT 06117, USA.
Biology (Basel). 2023 Jan 19;12(2):155. doi: 10.3390/biology12020155.
Synucleins consist of three proteins exclusively expressed in vertebrates. α-Synuclein (αS) has been identified as the main proteinaceous aggregate in Lewy bodies, a pathological hallmark of many neurodegenerative diseases. Less is understood about β-synuclein (βS) and γ-synuclein (γS), although it is known βS can interact with αS in vivo to inhibit aggregation. Likewise, both γS and βS can inhibit αS's propensity to aggregate in vitro. In the central nervous system, βS and αS, and to a lesser extent γS, are highly expressed in the neural presynaptic terminal, although they are not strictly located there, and emerging data have shown a more complex expression profile. Synapse loss and astrocyte atrophy are early aspects of degenerative diseases of the brain and correlate with disease progression. Synucleins appear to be involved in synaptic transmission, and astrocytes coordinate and organize synaptic function, with excess αS degraded by astrocytes and microglia adjacent to the synapse. βS and γS have also been observed in the astrocyte and may provide beneficial roles. The astrocytic responsibility for degradation of αS as well as emerging evidence on possible astrocytic functions of βS and γS, warrant closer inspection on astrocyte-synuclein interactions at the synapse.
突触核蛋白由三种仅在脊椎动物中表达的蛋白质组成。α-突触核蛋白(αS)已被确定为路易小体中的主要蛋白质聚集体,路易小体是许多神经退行性疾病的病理标志。关于β-突触核蛋白(βS)和γ-突触核蛋白(γS)的了解较少,尽管已知βS在体内可与αS相互作用以抑制聚集。同样,γS和βS在体外均可抑制αS的聚集倾向。在中枢神经系统中,βS和αS,以及程度较轻的γS,在神经突触前末端高度表达,尽管它们并不严格局限于该部位,并且新出现的数据显示其表达谱更为复杂。突触丧失和星形胶质细胞萎缩是脑部退行性疾病的早期表现,且与疾病进展相关。突触核蛋白似乎参与突触传递,星形胶质细胞协调并组织突触功能,多余的αS由突触附近的星形胶质细胞和小胶质细胞降解。在星形胶质细胞中也观察到了βS和γS,它们可能发挥有益作用。星形胶质细胞对αS的降解作用以及关于βS和γS可能的星形胶质细胞功能的新证据,使得有必要更深入地研究突触处星形胶质细胞与突触核蛋白的相互作用。