Targeting mitochondrial dysfunction to salvage cellular senescence for managing neurodegeneration

Komal Sharma; Joyobrata Sarkar; Anchal Trisal; Rishika Ghosh; Anubhuti Dixit; Abhishek Kumar Singh

doi:10.1016/bs.apcsb.2023.02.016

Targeting mitochondrial dysfunction to salvage cellular senescence for managing neurodegeneration

Adv Protein Chem Struct Biol. 2023:136:309-337. doi: 10.1016/bs.apcsb.2023.02.016. Epub 2023 May 22.

Authors

Komal Sharma¹, Joyobrata Sarkar¹, Anchal Trisal¹, Rishika Ghosh¹, Anubhuti Dixit², Abhishek Kumar Singh³

Affiliations

¹ Amity Institute of Neuropsychology and Neurosciences, Amity University Uttar Pradesh, Noida, India.
² Amity Institute of Neuropsychology and Neurosciences, Amity University Uttar Pradesh, Noida, India. Electronic address: adixit3@amity.edu.
³ Amity Institute of Neuropsychology and Neurosciences, Amity University Uttar Pradesh, Noida, India. Electronic address: aks84m@gmail.com.

PMID: 37437982
DOI: 10.1016/bs.apcsb.2023.02.016

Abstract

Aging is an inevitable phenomenon that causes a decline in bodily functions over time. One of the most important processes that play a role in aging is senescence. Senescence is characterized by accumulation of cells that are no longer functional but elude the apoptotic pathway. These cells secrete inflammatory molecules that comprise the senescence associated secretory phenotype (SASP). Several essential molecules such as p53, Rb, and p16INK4a regulate the senescence process. Mitochondrial regulation has been found to play an important role in senescence. Reactive oxygen species (ROS) generated from mitochondria can affect cellular senescence by inducing the persistent DNA damage response, thus stabilizing the senescence. Evidently, senescence plays a major contributory role to the development of age-related neurological disorders. In this chapter, we discuss the role of senescence in the progression and onset of several neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. Moreover, we also discuss the efficacy of certain molecules like MitoQ, SkQ1, and Latrepirdine that could be proven therapeutics with respect to these disorders by regulating mitochondrial activity.

Keywords: Mitochondrial dysfunction; Neurodegeneration; Senescence; Senolytics; Senotherapeutics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease*
Cellular Senescence*
Cyclin-Dependent Kinase Inhibitor Proteins
Humans
Mitochondria

Substances

Cyclin-Dependent Kinase Inhibitor Proteins