Proteolytic α-Synuclein Cleavage in Health and Disease.
Proteolytic α-Synuclein Cleavage in Health and Disease.
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DOI：
10.3390/ijms22115450
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发表时间：
2021-05-21
影响因子：
5.6
通讯作者：
Roßner S
中科院分区：
文献类型：
--
作者：
Bluhm A;Schrempel S;von Hörsten S;Schulze A;Roßner S
在帕金森病中，路易体和路易神经突内 α-突触核蛋白的聚集代表了神经病理学标志。然而，触发寡聚和原纤维 α-突触核蛋白聚集的细胞和分子机制尚不完全清楚。最近的证据表明，金属离子和翻译后修饰（例如磷酸化、泛素化、硝化、糖化和 SUMOylation）诱导的氧化应激会影响 α-突触核蛋白构象及其聚集倾向和神经毒性特征。此外，特定蛋白酶对 α-突触核蛋白的蛋白水解裂解导致形成广谱片段，这些片段具有连续改变且尚未完全了解的生理和/或病理特性。在本综述中，我们总结了健康和疾病中神经素、钙蛋白酶-1、组织蛋白酶 D 和基质金属蛋白酶-3 蛋白水解 α-突触核蛋白裂解的最新知识。我们还阐明了相同酶对阿尔茨海默病致病蛋白的蛋白水解加工的贡献，并报告了致病蛋白聚集的潜在跨疾病机制。
In Parkinson’s disease, aggregates of α-synuclein within Lewy bodies and Lewy neurites represent neuropathological hallmarks. However, the cellular and molecular mechanisms triggering oligomeric and fibrillary α-synuclein aggregation are not fully understood. Recent evidence indicates that oxidative stress induced by metal ions and post-translational modifications such as phosphorylation, ubiquitination, nitration, glycation, and SUMOylation affect α-synuclein conformation along with its aggregation propensity and neurotoxic profiles. In addition, proteolytic cleavage of α-synuclein by specific proteases results in the formation of a broad spectrum of fragments with consecutively altered and not fully understood physiological and/or pathological properties. In the present review, we summarize the current knowledge on proteolytical α-synuclein cleavage by neurosin, calpain-1, cathepsin D, and matrix metalloproteinase-3 in health and disease. We also shed light on the contribution of the same enzymes to proteolytical processing of pathogenic proteins in Alzheimer’s disease and report potential cross-disease mechanisms of pathogenic protein aggregation.
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影响因子：
3.6
作者：
Cullen, Valerie;Lindfors, Maria;Ng, Juliana;Paetau, Anders;Swinton, Erika;Kolodziej, Piotr;Boston, Heather;Saftig, Paul;Woulfe, John;Feany, Mel B.;Myllykangas, Liisa;Schlossmacher, Michael G.;Tyynela, Jaana
通讯作者：
Tyynela, Jaana
影响因子：
12.7
作者：
Bouter Y;Dietrich K;Wittnam JL;Rezaei-Ghaleh N;Pillot T;Papot-Couturier S;Lefebvre T;Sprenger F;Wirths O;Zweckstetter M;Bayer TA
通讯作者：
Bayer TA
影响因子：
6
作者：
Casas, C;Sergeant, N;Pradier, L
通讯作者：
Pradier, L
影响因子：
5.5
作者：
Bunk J;Prieto Huarcaya S;Drobny A;Dobert JP;Walther L;Rose-John S;Arnold P;Zunke F
通讯作者：
Zunke F
影响因子：
5.3
作者：
Braak, Heiko;Del Tredici, Kelly
通讯作者：
Del Tredici, Kelly