Biotechnology Research and Training Center, University of North Carolina-Pembroke, Pembroke, NC, United States.
Department of Biology and Marine Biology, University of North Carolina-Wilmington, Wilmington, NC, United States.
Int Rev Neurobiol. 2020;154:303-324. doi: 10.1016/bs.irn.2020.02.012. Epub 2020 Jul 10.
The endosomal-lysosomal pathways and related autophagic processes are responsible for proteostasis, involving complexes between lysosomes and autophagosomes. Lysosomes are a key component of homeostasis, involved in cell signaling, metabolism, and quality control, and they experience functional compromise in metabolic diseases, aging, and neurodegenerative diseases. Many genetic mutations and risk factor genes associated with proteinopathies, as well as with metabolic diseases like diabetes, negatively influence endocytic trafficking and autophagic clearance. In contrast, health-improving exercise induces autophagy-lysosomal degradation, perhaps promoting efficient digestion of injured organelles so that undamaged organelles ensure cellular healthiness. Reductions in lysosomal hydrolases are implicated in Alzheimer's, Parkinson's, and lysosomal storage diseases, as well as obesity-related pathology, and members of the cathepsin enzyme family are involved in clearing both Aβ42 and α-synuclein. Upregulation of cathepsin hydrolases improves synaptic and memory functions in models of dementia and in exercising humans, thus identifying lysosomal-related systems as vital for healthy cognitive aging.
内体溶酶体途径和相关的自噬过程负责蛋白质稳态，涉及溶酶体和自噬体之间的复合物。溶酶体是体内平衡的关键组成部分，参与细胞信号转导、代谢和质量控制，并且在代谢疾病、衰老和神经退行性疾病中经历功能障碍。许多与蛋白病以及糖尿病等代谢疾病相关的遗传突变和风险因素基因，会对内吞作用和自噬清除产生负面影响。相反，有益健康的运动诱导自噬溶酶体降解，可能促进受损细胞器的有效消化，从而使未受损的细胞器确保细胞健康。溶酶体水解酶的减少与阿尔茨海默病、帕金森病和溶酶体贮积病以及与肥胖相关的病理学有关，组织蛋白酶酶家族的成员参与清除 Aβ42 和 α-突触核蛋白。组织蛋白酶水解酶的上调改善了痴呆症模型和运动人群中的突触和记忆功能，从而确定了与溶酶体相关的系统对健康认知衰老至关重要。
