ACSS2-dependent histone acetylation improves cognition in mouse model of Alzheimer's disease.
Yingbin LinAnlan LinLili CaiWeibin HuangShanzhi YanYuanxiang WeiXinglin RuanWenting FangXiaoman DaiJinbo ChengJie ZhangWanjin ChenQinyong YeXiaochun ChenJing ZhangPublished in: Molecular neurodegeneration (2023)
ACSS2 is a key molecular switch of cognitive impairment and that targeting ACSS2 or acetate administration may serve as a novel therapeutic strategy for the treatment of intermediate or advanced AD. Nuclear acetyl-CoA pools are generated partly from local acetate that is metabolized by acetyl-CoA synthetase 2 (ACSS2). Model depicts that ACSS2 expression is downregulated in the brains of 5×FAD model mice and AD patients. Of note, ACSS2 downregulation mediates a reduction in ionotropic glutamate receptor expression through histone acetylation, which exacerbates synaptic plasticity impairment in AD. These deficits can be rescued by ACSS2 upregulation or acetate supplementation (GTA, an FDA-approved food additive), which may serve as a promising therapeutic strategy for AD treatment.
Keyphrases
- mouse model
- cognitive impairment
- poor prognosis
- end stage renal disease
- dna methylation
- cell proliferation
- chronic kidney disease
- newly diagnosed
- signaling pathway
- ejection fraction
- traumatic brain injury
- prognostic factors
- drug delivery
- type diabetes
- metabolic syndrome
- multiple sclerosis
- replacement therapy
- risk assessment
- patient reported