Exploring the nexus of cGAS STING pathway in neurodegenerative terrain: A therapeutic odyssey.

Autor: Sharma O; Chitkara College of Pharmacy, Chitkara University, Rajpura 140401, Punjab, India., Kaur Grewal A; Chitkara College of Pharmacy, Chitkara University, Rajpura 140401, Punjab, India. Electronic address: amarjot.kaur@chitkara.edu.in., Khan H; Chitkara College of Pharmacy, Chitkara University, Rajpura 140401, Punjab, India., Gurjeet Singh T; Chitkara College of Pharmacy, Chitkara University, Rajpura 140401, Punjab, India.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2024 Dec 05; Vol. 142 (Pt B), pp. 113205. Date of Electronic Publication: 2024 Sep 27.
DOI: 10.1016/j.intimp.2024.113205
Abstrakt: By detecting and responding to cytosolic DNA, the cGAS STING pathway regulates the innate immune responses bymediatinginflammatory reactions and antiviral defense. Thederegulation and modification of this system have been linked to variousneurodegenerative diseases like AD, PD and ALS. Accumulation of tau protein and Aβ aggregates to activate the pathway and releases neuroinflammatory cytokines which accelerates neuronal dysfunction and cognitive impairment as the symptom of AD. Similarly, in PD Alpha-synuclein aggregates activate the cGAS STING pathway and regulate the neuroinflammation and oxidative stress. In ALS, mutation of the genes causes the activation of the pathway which leads to motor neuron degeneration. Alteration of the cGAS STING pathway also leads to mitochondrial dysfunction and impaired autophagy. Preclinical investigations of AD, PD, and ALS animal models showed that STING pathway inhibitors reduced inflammation and improved neurological outcomes and modulators of the cGAS STING pathway may treat these neurodegenerative disorders. In this review we focus on the fact thatneuroinflammation, neuronal dysfunction, and various disease progressions can be treated byaltering the cGAS STING pathway. Understanding the processes and creating specific interventions for this route may offer new treatments for these terrible illnesses.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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