Caspase-mediated regulation of the distinct signaling pathways and mechanisms in neuronal survival

• Published in: International immunopharmacology 2022-09, Vol.110, p.108951-108951, Article 108951
• Main Authors: Khan, Heena, Bangar, Annu, Grewal, Amarjot Kaur, Bansal, Puneet, Singh, Thakur Gurjeet
• Format: Article
• Language: English
• Subjects: Apoptosis activation; Caspases; Endoplasmic reticulum stress; Mitochondrial dysfunction; Neuronal injury
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2022.108951

•Caspases elicit and propagate signalling events that result in cellular death.•Caspases are cysteine proteases maintaining the homeostasis of the cell.•Caspases have been implicated in apoptotic neuronal death following acute brain damage.•Caspases inhibition is a potential target to provide neuroprotection.•Agents altering ER-mediated Ca2+ ion control have been linked to mitochondrial dysfunction and caspase activation. Caspases are intimately associated with altering various signaling pathways, resulting in programmed cell death or apoptosis. Apoptosis is necessary for the normal homeostasis of cells and their development. The untoward activation of apoptotic pathways indirectly or directly results in pathologies of various diseases. Identifying different caspases in apoptotic pathways directed the research to develop caspase inhibitors as therapeutic agents. However, no drug is available in the market that targets caspase inhibition and produces a therapeutic effect. Here, we will shed light on the role of caspases in the number of neuronal disorders and neurodegenerative diseases. The article reviews the findings about the activation of various upstream mechanisms associated with caspases in neurodegenerative disorders along with the recent progress in the generation of caspase inhibitors and the challenge faced in their development as therapeutic agents for neurological indications.