Autophagy–Proteasome Crosstalk in Neurodegenerative Diseases: Cellular Proteostasis, Neural Interactions, and Therapeutic Implications

Neurodegenerative conditions such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis (ALS) are devastating disorders with the gradual loss of neurons and cognitive or motor disability. This is a review article that develops the crucial functions of autophagy and proteostasis within the scope of the neurodegenerative disease. Autophagy is a very well-conserved cell process that poses a quality control checkpoint that allows for the degradation and recycling of damaged organelles and misfolded proteins. Chaperones, the ubiquitin–proteasome complexes, and endoplasmic reticulum-associated degradation (ERAD) are also referred to as proteostasis, which plays a key role in ensuring the correct protein folding properties and the prevention of toxic protein accumulation. This article offers a detailed discussion of the relationship between autophagy and proteostasis, illustrating the mechanisms of mutual cooperation of these processes, ensuring cellular homeostasis and inhibiting the formation of pathogenic protein aggregates. In addition, this review includes experimental data during preclinical studies and clinical trials and expounds on the therapeutic opportunities that show the potential of targeting autophagy and proteostasis to counter neurodegenerative disorders. Although research progress creates potential for new indicators, the issues and difficulties relating to the effects of regulating such complex cellular pathways are also discussed in the article. Finally, the review can add to the research of neurodegenerative disease mechanisms of autophagy and proteostasis as well as provide insights about the future of treatment and its implementation.