Natural Products in Therapeutic Management of Multineurodegenerative Disorders by Targeting Autophagy.

Sibhghatulla Shaikh,Inho Choi,Mirza Masroor Ali Beg,Khurshid Ahmad,Jeong Ho Lim,Syed Sayeed Ahmad,Eun Ju Lee,Amit K Verma,Xinfeng Li

doi:10.1155/2021/6347792

Abstract

Autophagy is an essential cellular process that involves the transport of cytoplasmic content in double-membraned vesicles to lysosomes for degradation. Neurons do not undergo cytokinesis, and thus, the cell division process cannot reduce levels of unnecessary proteins. The primary cause of neurodegenerative disorders (NDs) is the abnormal deposition of proteins inside neuronal cells, and this could be averted by autophagic degradation. Thus, autophagy is an important consideration when considering means of developing treatments for NDs. Various pharmacological studies have reported that the active components in herbal medicines exhibit therapeutic benefits in NDs, for example, by inhibiting cholinesterase activity and modulating amyloid beta levels, and α-synuclein metabolism. A variety of bioactive constituents from medicinal plants are viewed as promising autophagy controllers and are revealed to recover the NDs by targeting the autophagic pathway. In the present review, we discuss the role of autophagy in the therapeutic management of several NDs. The molecular process responsible for autophagy and its importance in various NDs and the beneficial effects of medicinal plants in NDs by targeting autophagy are also discussed.

Highlights

Autophagy is a fundamental, exceptionally well-controlled process in the eukaryotic cell recycling system under different states of cellular stress
Many neurodegenerative diseases (NDs) are linked with inflammatory responses in glia, which may contribute to pathology, and autophagy in glial cells may play a role in regulating these processes [53]
Α-synuclein mutation has been suggested to impair chaperone-mediated autophagy (CMA) [76, 81]. These results indicate that the regulations of more than one type of autophagy by α-synuclein mutations have toxic effects on neuronal cells

Summary

Introduction

Exceptionally well-controlled process in the eukaryotic cell recycling system under different states of cellular stress. There are typically three types of autophagy: macroautophagy, microautophagy, and chaperone-mediated autophagy (CMA), all of which have specific roles that depend on the cellular microenvironment, signals, and organs, but all usually involve proteolytic degradation of cytosolic components inside lysosomes [7]. CMA is an extensive form of autophagy found in almost all cells and tissue types in higher eukaryotes and involves the direct recognition of targeted proteins containing the KFERQ motif, which is recognized by chaperone proteins, such as the heat shock protein (Hsc-70). These proteins are delivered directly to lysosomes via the lysosomal-associated membrane protein 2A (LAMP-2A) [11, 12]. Before describing the roles of herbal products in NDs, we provide a brief overview of autophagic processes at a molecular level and their roles in various NDs

Molecular Process of Autophagy

Autophagy and Neurodegenerative Disorders

Beneficial Effects of Medicinal Plants on NDs by Targeting Autophagy

Conclusion and Future Prospects

Conflicts of Interest