神经退行性变
溶酶体
自噬
组织蛋白酶
生物
亨廷顿蛋白
亨廷顿病
细胞生物学
神经元蜡样脂褐素沉着症
组织蛋白酶D
神经科学
疾病
医学
生物化学
病理
酶
细胞凋亡
基因
作者
Alice Drobny,Susy Prieto Huarcaya,Jan Philipp Dobert,Annika Kluge,Josina Bunk,Theresia Schlothauer,Friederike Zunke
标识
DOI:10.1016/j.bbamcr.2022.119243
摘要
Lysosomes are ubiquitous organelles with a fundamental role in maintaining cellular homeostasis by mediating degradation and recycling processes. Cathepsins are the most abundant lysosomal hydrolyses and are responsible for the bulk degradation of various substrates. A correct autophagic function is essential for neuronal survival, as most neurons are post-mitotic and thus susceptible to accumulate cellular components. Increasing evidence suggests a crucial role of the lysosome in neurodegeneration as a key regulator of aggregation-prone and disease-associated proteins, such as α-synuclein, β-amyloid and huntingtin. Particularly, alterations in lysosomal cathepsins CTSD, CTSB and CTSL can contribute to the pathogenesis of neurodegenerative diseases as seen for neuronal ceroid lipofuscinosis, synucleinopathies (Parkinson's disease, Dementia with Lewy Body and Multiple System Atrophy) as well as Alzheimer's and Huntington's disease. In this review, we provide an overview of recent evidence implicating CTSD, CTSB and CTSL in neurodegeneration, with a special focus on the role of these enzymes in α-synuclein metabolism. In addition, we summarize the potential role of lysosomal cathepsins as clinical biomarkers in neurodegenerative diseases and discuss potential therapeutic approaches by targeting lysosomal function.
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