Brain-protective mechanisms of autophagy associated circRNAs: Kick starting self-cleaning mode in brain cells via circRNAs as a potential therapeutic approach for neurodegenerative diseases

Abstract

Altered autophagy is a hallmark of neurodegeneration but how autophagy is regulated in the brain and dysfunctional autophagy leads to neuronal death has remained cryptic. Being a key cellular waste-recycling and housekeeping system, autophagy is implicated in a range of brain disorders and altering autophagy flux could be an effective therapeutic strategy and has the potential for clinical applications down the road. Tight regulation of proteins and organelles in order to meet the needs of complex neuronal physiology suggests that there is distinct regulatory pattern of neuronal autophagy as compared to non-neuronal cells and nervous system might have its own separate regulator of autophagy. Evidence has shown that circRNAs participates in the biological processes of autophagosome assembly. The regulatory networks between circRNAs, autophagy, and neurodegeneration remains unknown and warrants further investigation. Understanding the interplay between autophagy, circRNAs and neurodegeneration requires a knowledge of the multiple steps and regulatory interactions involved in the autophagy pathway which might provide a valuable resource for the diagnosis and therapy of neurodegenerative diseases. In this review, we aimed to summarize the latest studies on the role of brain-protective mechanisms of autophagy associated circRNAs in neurodegenerative diseases (including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, Spinal Muscular Atrophy, Amyotrophic Lateral Sclerosis, and Friedreich’s ataxia) and how this knowledge can be leveraged for the development of novel therapeutics against them. Autophagy stimulation might be potential one-size-fits-all therapy for neurodegenerative disease as per considerable body of evidence, therefore future research on brain-protective mechanisms of autophagy associated circRNAs will illuminate an important feature of nervous system biology and will open the door to new approaches for treating neurodegenerative diseases.

Circular RNA in Multiple Sclerosis: Pathogenicity and Potential Biomarker Development: A Systematic Review

“…Some of these papers barely mentioned circRNA, 64,[86][87][88][89][90][91][92] while others focused on other types of ncRNAs such as miRNA and LncRNA. 93,94 A few papers discussed the role of circRNA in other types of diseases but did not mention MS. [95][96][97][98] The lack of comprehensive discussion on the role of circRNA in MS and other diseases may be attributed to the limited understanding of this molecule. Further research is needed to fully elucidate the functions of circRNA in health and disease, particularly in the context of complex diseases such as MS.…”

The role of cellular senescence in neurodegenerative diseases

“…Autophagy is the primary intracellular mechanism underlying the degradation of accumulated misfolded proteins (Zhang et al 2021). Defects in the autophagic pathway are associated with NDs at various stages; however, the exact autophagy regulation mechanism in the brain remains enigmatic (Basri et al 2022). Furthermore, oxidative stress, metal-ion disorders, energy metabolism disorders, and immune inflammation contribute to ND pathogenesis (Rajesh and Kanneganti 2022;Zhang et al 2023b).…”