cGAS-STING triggers inflammaging-associated neurodegeneration

Abstract

In their recent article in Nature, Gulen et al. [1] established the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway as a regulatory driver of inflammaging-associated neurodegeneration in mice. Pharmacological blockade of this pathway in aged mice prevented inflammaging and improved cognitive and motor performance. In the same vein, chemical intervention attenuated a toxic murine model of cGAS gain-of-function in microglia leading to neuroinflammation, neurotoxicity and impaired memory capacity. These observations point to cGAS-STING as a targetable molecular sensor in human immunosenescence, aged-related inflammation and neurodegeneration.