Gladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA 94158, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA.
Biotechnology Research and Training Center, University of North Carolina at Pembroke, Pembroke, NC, USA.
Curr Opin Neurobiol. 2018 Feb;48:52-58. doi: 10.1016/j.conb.2017.09.005. Epub 2017 Oct 10.
Endo-lysosomal pathways are essential in maintaining protein homeostasis in the cell. Numerous genes in the endo-lysosomal pathways have been found to associate with neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and frontotemporal dementia (FTD). Mutations of these genes lead to dysfunction in multiple steps of the endo-lysosomal network: autophagy, endocytic trafficking and lysosomal degradation, resulting in accumulation of pathogenic proteins. Although the exact pathogenic mechanism varies for different disease-associated genes, dysfunction of the endo-lysosomal pathways represents a converging mechanism shared by these diseases. Therefore, strategies that correct or compensate for endo-lysosomal dysfunction may be promising therapeutic approaches to treat neurodegenerative diseases.
内体溶酶体途径对于维持细胞内蛋白质的稳态至关重要。内体溶酶体途径中的许多基因已被发现与神经退行性疾病有关,包括阿尔茨海默病(AD)、帕金森病(PD)和额颞叶痴呆(FTD)。这些基因的突变导致内体溶酶体网络的多个步骤功能失调:自噬、内吞运输和溶酶体降解,导致致病性蛋白的积累。尽管不同疾病相关基因的具体致病机制不同,但内体溶酶体途径的功能障碍代表了这些疾病的一个共同的趋同机制。因此,纠正或补偿内体溶酶体功能障碍的策略可能是治疗神经退行性疾病的有前途的治疗方法。