Current Status of Autophagy Enhancers in Metabolic Disorders and Other Diseases.

Kihyoun Park,Myung-Shik Lee

doi:10.3389/fcell.2022.811701

Abstract

Autophagy is pivotal in the maintenance of organelle function and intracellular nutrient balance. Besides the role of autophagy in the homeostasis and physiology of the individual tissues and whole organism in vivo, dysregulated autophagy has been incriminated in the pathogenesis of a variety of diseases including metabolic diseases, neurodegenerative diseases, cardiovascular diseases, inflammatory or immunological disorders, cancer and aging. Search for autophagy modulators has been widely conducted to amend dysregulation of autophagy or pharmacologically modulate autophagy in those diseases. Current data support the view that autophagy modulation could be a new modality for treatment of metabolic syndrome associated with lipid overload, human-type diabetes characterized by deposition of islet amyloid or other diseases including neurodegenerative diseases, infection and cardiovascular diseases. While clinically available bona fide autophagy modulators have not been developed yet, it is expected that on-going investigation will lead to the development of authentic autophagy modulators that can be safely administered to patients in the near future and will open a new horizon for treatment of incurable or difficult diseases.

Highlights

Autophagy, derived from Greek words meaning “self-devouring,” is a cellular process of degradation of cell’s own material including organelles, proteins or cellular fluid in lysosome acting as the effector organelle of autophagic degradation (Mizushima and Komatsu, 2011; Agudo-Canalejo et al, 2021)
As detailed molecular mechanisms of selective autophagy are being discovered, specific modulation of specialized aspects of autophagy possibly at the specific tissues or sites will not be a remote possibility, which will be of a paramount importance for clinical application of autophagy modulators
Some caution might be exercised in the use of autophagy enhancer for treatment of human diseases

Summary

Introduction

Autophagy, derived from Greek words meaning “self-devouring,” is a cellular process of degradation of cell’s own material including organelles, proteins or cellular fluid in lysosome acting as the effector organelle of autophagic degradation (Mizushima and Komatsu, 2011; Agudo-Canalejo et al, 2021). While these results showed improvement of metabolic profile of HFD-fed mice through enhanced clearance of lipid and reduced inflammasome activation, another potential metabolic effect of MSL-7 was studied because amyloidogenic hIAPP oligomer or islet amyloid (Westermark et al, 2011), is preferentially cleared by autophagy or lysosomal proteolysis rather than proteasomal degradation (Rubinsztein, 2006; Kim et al, 2014).

Results

Conclusion