Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, Heraklion, 70013, Greece.
Department of Basic Sciences, Faculty of Medicine, University of Crete, Heraklion, 71500, Greece.
Biotechnol J. 2020 Aug;15(8):e1900267. doi: 10.1002/biot.201900267. Epub 2020 Mar 18.
Imbalance between the main intracellular degradative, trafficking and intercellular shuttling pathways has been implicated in disease pathogenesis. Autophagy controls degradation of cellular components, while vesicular trafficking permits transport of material in and out of the cell. Emerging evidence has uncovered the extensive interconnectivity between these pathways, which is crucial to maintain organismal homeostasis. Thus, therapeutic intervention and drug development strategies targeting these processes, particularly in neurodegeneration, should account for this broad crosstalk, to maximize effectiveness. Here, recent findings underlining the highly dynamic nature of the crosstalk between autophagy, endosomal transport, and secretion is reviewed. Synergy of autophagy and endosomes for degradation, as well as, competition of autophagy and secretion are discussed. Perturbation of this crosstalk triggers pathology especially neurodegeneration.
细胞内主要的降解、运输和细胞间转运途径之间的失衡与疾病的发病机制有关。自噬控制着细胞成分的降解，而囊泡运输则允许物质在细胞内外运输。新出现的证据揭示了这些途径之间的广泛相互联系，这对于维持生物体的内稳态至关重要。因此，针对这些过程的治疗干预和药物开发策略，特别是在神经退行性疾病中，应该考虑到这种广泛的串扰，以最大限度地提高疗效。在这里，我们回顾了强调自噬、内体运输和分泌之间高度动态串扰的最新发现。自噬和内体协同降解，以及自噬和分泌竞争的情况进行了讨论。这种串扰的破坏会引发病理学，特别是神经退行性变。
