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

By detecting and responding to cytosolic DNA, the cGAS STING pathway regulates the innate immune responses by mediating inflammatory reactions and antiviral defense. The deregulation and modification of this system have been linked to various neurodegenerative diseases like AD, PD and ALS. Accumulation of tau protein and A beta 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 that neuroinflammation, neuronal dysfunction, and various disease progressions can be treated by altering the cGAS STING pathway. Understanding the processes and creating specific interventions for this route may offer new treatments for these terrible illnesses.