Autophagy and autophagy‐related molecules in neurodegenerative diseases

Abstract

Autophagy is one of the degradation pathways to remove proteins or damaged organelles in cells that plays an important role in neuroprotection. Different stages of autophagy are regulated by autophagy‐related genes, and many molecules such as transcription factor EB (TFEB) are involved. The complete autophagy process plays an important role in maintaining the dynamic balance of autophagy and is crucial to the homeostasis of intracellular substance and energy metabolism. Autophagy balance is disrupted in neurodegenerative diseases, accounting for a variety of degeneration disorders. These impairments can be alleviated or treated by the regulation of autophagy through molecules such as TFEB.

Novel Insights into The Roles of N6-methyladenosine (m6A) Modification and Autophagy in Human Diseases

“…Firstly, m 6 A levels, which play diverse roles in various physiological statuses, differ in different cells and/or disease progression stages [37,121]. Second, the function of autophagy is context-dependent and highly affected by the disease status and exposure to external stimuli [122,123]. Hence, more research is warranted to investigate the functions and molecular regulatory mechanisms of the association between m 6 A regulators and autophagy.…”

The Role of Autophagy in the Development of Pathological Conditions of the Body

“…Misfolded proteins were found to prevent TFEB inactivation, thus significantly increasing the expression of the genes they regulate. In neurodegenerative diseases, this can be considered a cell compensatory response to a decrease in autophagy efficiency [ 16 ].…”

“…In normal conditions, PINK1 is transported to the mitochondrial matrix by TOM/TIM translocases, where it is degraded by the proteases PARL and MRR ( Fig. 3 ) [ 16 ].…”

“…Установлено также, что мисфолдинг-белки препятствуют инактивации TFEB, вызывая тем самым значительное увеличение экспрессии контролируемых ими генов. При нейродегенеративных процессах это можно рассматривать как компенсаторную реакцию клетки на снижение эффективности аутофагии[16].Фактор транскрипции TFEB также участвует в регуляции белка PINK1 -серин/треониновой киназы, отвечающей за локализацию убиквитинлигазы паркин на внешней мембране митохондрий, вызванную снижением мембранного потенциала поврежденных митохондрий. Белок паркин полиубиквитинирует белки внешней мембраны митохондрий (ОMM), что приводит к образованию сложного белкового ОММ/polyUb-p62-LC3II-комплекса, необходимого для связывания аутофагосомы с ми-Рис.…”