Autophagy Intertwines with Different Diseases—Recent Strategies for Therapeutic Approaches

Abstract

Autophagy is a regular and substantial “clear-out process” that occurs within the cell and that gets rid of debris that accumulates in membrane-enclosed vacuoles by using enzyme-rich lysosomes, which are filled with acids that degrade the contents of the vacuoles. This machinery is well-connected with many prevalent diseases, including cancer, HIV, and Parkinson’s disease. Considering that autophagy is well-known for its significant connections with a number of well-known fatal diseases, a thorough knowledge of the current findings in the field is essential in developing therapies to control the progression rate of diseases. Thus, this review summarizes the critical events comprising autophagy in the cellular system and the significance of its key molecules in manifesting this pathway in various diseases for down- or upregulation. We collectively reviewed the role of autophagy in various diseases, mainly neurodegenerative diseases, cancer, inflammatory diseases, and renal disorders. Here, some collective reports on autophagy showed that this process might serve as a dual performer: either protector or contributor to certain diseases. The aim of this review is to help researchers to understand the role of autophagy-regulating genes encoding functional open reading frames (ORFs) and its connection with diseases, which will eventually drive better understanding of both the progression and suppression of different diseases at various stages. This review also focuses on certain novel therapeutic strategies which have been published in the recent years based on targeting autophagy key proteins and its interconnecting signaling cascades.

Roles of PRR-Mediated Signaling Pathways in the Regulation of Oxidative Stress and Inflammatory Diseases

“…Increasing evidence has shown that targeting ROS/NADPH oxidase, NLRP3 inflammasome, MAPK/NF-κB signaling, Nrf2 signaling, autophagy, and mitochondrial bioenergetics provides potential therapeutic strategies for the prevention and treatment of various inflammatory diseases [ 15 , 137 , 138 , 139 , 140 , 141 , 142 ]. However, given the multifactorial etiology of inflammatory diseases and the limited success of antioxidant therapies achieved to date, therapeutic targets at single risk factor interventions are not enough to block the progression of inflammatory diseases.…”

Case of Early-Onset Parkinson’s Disease in a Heterozygous Mutation Carrier of the ATP7B Gene

“…About 5–10% of PD cases have Mendelian inheritance [21,22]. There are about 20 genes with the mutations that are known to be responsible for disturbances in the cellular processes leading to neuronal death in SNpc, including mitochondrial dysfunction, defects in mitoautophagy and chaperone-mediated autophagy, defective dopamine metabolism, endoplasmic reticulum stress from protein aggregation, and mitochondrial calcium transport [23,24,25,26]. The remaining 90% of PD cases are typically classified as sporadic, which are believed to be caused by a combination of multiple etiological factors, including oxidative stress, and adverse and harmful environmental factors that are not fully understood [27].…”

Lysophosphatidic acid reverses Temsirolimus-induced changes in lipid droplets and mitochondrial networks in renal cancer cells

“…Suboptimal or ineffective cellular responses to mTOR inhibitors may be due to activation of cytoprotective pathways including autophagic flux [9,30,31,47]. We now demonstrate that the autophagic flux inhibitor (HCQ) alters LD abundance in both malignant and normal renal cell lines (Fig 5C).…”