Table 1 Therapeutic approaches targeting cGAS-STING pathway for neurodegenerative diseases

Disease	Intervention	Mechanism	Result	Reference
AD	NR	Stimulate mitophagy, and reduce mtDNA release and cGAS activation	NR supplementation improved cognitive and synaptic functions in APP/PS1 mutant mice.	[9]
HD	Melatonin	Decrease mitochondrial oxidative stress, reduce cytosolic DNA and decrease inflammation	Melatonin inhibited mtDNA-induced neuroinflammation in aralkylamine N-acetyltransferase knockout mice.	[10]
PD	Mdivi-1	Decrease mitochondrial fission, and reduce mtDNA leakage and cGAS activation	Mdivi-1 treatment inhibited DRP1 and maintained mitochondria membrane potential in Lrrk2 knockout macrophages.	[12]
AT	H-151	Inhibit STING	H-151 efficiently inhibited SASP expression, ameliorated astrocyte senescence, and alleviated A-T brain organoid neuropathology.	[13]
MS	Ganciclovir	Inhibit microglial reactivity and neuroinflammation	Ganciclovir (GCV) inhibited inflammation in MS mouse model dependent on STING-mediated IFN-1 response.	[14]
ALS	H-151	Inhibit STING, and decrease IFN-1 and NF-κB expressions	H-151 prevented neurons loss, ameliorating disease progression in ALS mouse model.	[15]

AD: Alzheimer’s disease; HD: Huntington’s disease; PD: Parkinson’s disease; AT: Ataxia-Telangiectasia; MS: multiple sclerosis; ALS: amyotrophic lateral sclerosis.