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新兴自噬内溶酶体靶点在帕金森病治疗中的作用。

Emerging autophagic endo-lysosomal targets in the management of Parkinson's disease.

机构信息

Department of Pharmacology, SVKM's Doctor Bhanuben-Nanavati College of Pharmacy, Vile Parle (West), Mumbai, India.

Department of Pharmacology, SVKM's Doctor Bhanuben-Nanavati College of Pharmacy, Vile Parle (West), Mumbai, India.

出版信息

Rev Neurol (Paris). 2024 Jun;180(6):477-485. doi: 10.1016/j.neurol.2023.07.007. Epub 2023 Aug 14.

Abstract

Synucleopathies, specifically Parkinson's disease, are still incurable and available therapeutic options are scarce and symptomatic. The autophagy-lysosomal-endosomal system is an indigenous mechanism to manage the proteome. Excess/misfolded protein accumulation activates this system, which degrades the undesired proteins via lysosomes. Cells also eliminate these proteins by releasing them into the extracellular space via exosomes. However, the sutophagy-lysosomal-endosomal system becomes unfunctional in Parkinson's disease and there is accumulation and spread of pathogenic alpha-synuclein. Neuronal degeneration results Owing to pathogenic alpha-synuclein. Thus, the autophagy-lysosomal-endosomal system could be a promising target for neuroprotection. In the present review, we discuss the autophagy-lysosomal-endosomal system as an emerging target for the management of Parkinson's disease. Modulation of these targets associated with the autophagy-lysosomal-endosomal system can aid in clearing pathogenic alpha-synuclein and prevent the degeneration of neurons.

摘要

突触核蛋白病,特别是帕金森病,仍然无法治愈,可用的治疗方法很少,且只是对症治疗。自噬溶酶体内体系统是管理蛋白质组的固有机制。过量/错误折叠的蛋白质积累会激活该系统,通过溶酶体降解不需要的蛋白质。细胞还可以通过外泌体将这些蛋白质释放到细胞外空间来清除它们。然而,在帕金森病中,自噬溶酶体内体系统失去功能,并且致病性α-突触核蛋白会积累和扩散。由于致病性α-突触核蛋白的存在,神经元会退化。因此,自噬溶酶体内体系统可能是神经保护的一个有前途的靶点。在本综述中,我们讨论了自噬溶酶体内体系统作为管理帕金森病的一个新兴靶点。调节与自噬溶酶体内体系统相关的这些靶点可以帮助清除致病性α-突触核蛋白并防止神经元变性。

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