AUTHOR=Rai Sachchida Nand , Tiwari Neeraj , Singh Payal , Mishra Divya , Singh Anurag Kumar , Hooshmandi Etrat , Vamanu Emanuel , Singh Mohan P. 

TITLE=Therapeutic Potential of Vital Transcription Factors in Alzheimer’s and Parkinson’s Disease With Particular Emphasis on Transcription Factor EB Mediated Autophagy

JOURNAL=Frontiers in Neuroscience

VOLUME=Volume 15 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2021.777347

DOI=10.3389/fnins.2021.777347

ISSN=1662-453X

ABSTRACT=Autophagy is an important cellular self-digestion and recycling pathway that helps in maintaining cellular homeostasis. Deregulation at different steps of the autophagic and endolysosomal pathway has been reported to be associated with several neurodegenerative disorders such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington disease (HD) and is cited as a critically important feature for central nervous system (CNS) proteostasis. Recently, another molecular target for neurodegenerative disorders has been explored globally for their treatment. This is transcription factor EB (TFEB), which is a key regulator of autophagy and lysosomal biogenesis pathway. It has given rise to numerous research studies focused on exploring the therapeutic potential by targeting TFEB for the treatment of human diseases involving autophagy-lysosomal dysfunction, especially neurodegenerative disorders.
A common observation involving all neurodegenerative disorders is their poor efficacy to clear and recycle toxic aggregated proteins and damaged cellular organelles due to impairment in the autophagy pathway.  This dysfunction in autophagy characterized by the accumulation of toxic protein aggregates leads to a progressive loss in structural integrity/functionality of neurons and may even result in neuronal death.  In recent years, TFEB, a key regulator of autophagy & lysosomal biogenesis has received considerable attention. It has emerged as a potential therapeutic target in numerous neurodegenerative disorders like AD and PD. In various neurobiology studies involving animal models, TFEB has been found to ameliorate neurotoxicity and rescue neurodegeneration. Since TFEB is a master transcriptional regulator of autophagy and lysosomal biogenesis pathway and plays a crucial role in defining autophagy activation. Studies are been done to understand the mechanisms for TFEB dysfunction which may yield insights into how TFEB might be targeted and used for the therapeutic strategy for the development of a treatment process with extensive application to neurodegenerative disorders. In this review, we are trying to explore the role of different transcription factor-based targeted therapy by some natural compounds for AD and PD with special emphasis on TFEB.