Shati/Nat8l Overexpression Improves Cognitive Decline by Upregulating Neuronal Trophic Factor in Alzheimer's Disease Model Mice.
Kakeru ChinoNaotaka IzuoHiroshi NoikeKyosuke UnoTomoharu KuboyamaChihiro TohdaShin-Ichi MuramatsuAtsumi NittaPublished in: Neurochemical research (2022)
Alzheimer's disease (AD) is a type of dementia characterized by the deposition of amyloid β, a causative protein of AD, in the brain. Shati/Nat8l, identified as a psychiatric disease related molecule, is a responsive enzyme of N-acetylaspartate (NAA) synthesis. In the hippocampi of AD patients and model mice, the NAA content and Shati/Nat8l expression were reported to be reduced. Having recently clarified the involvement of Shati/Nat8l in cognitive function, we examined the recovery effect of the hippocampal overexpression of Shati/Nat8l in AD model mice (5XFAD). Shati/Nat8l overexpression suppressed cognitive dysfunction without affecting the Aβ burden or number of NeuN-positive neurons. In addition, brain-derived neurotrophic factor mRNA was upregulated by Shati/Nat8l overexpression in 5XFAD mice. These results suggest that Shati/Nat8l overexpression prevents cognitive dysfunction in 5XFAD mice, indicating that Shati/Nat8l could be a therapeutic target for AD.
Keyphrases
- cognitive decline
- high fat diet induced
- cell proliferation
- mild cognitive impairment
- transcription factor
- end stage renal disease
- insulin resistance
- wild type
- type diabetes
- ejection fraction
- chronic kidney disease
- mental health
- spinal cord injury
- spinal cord
- binding protein
- multiple sclerosis
- small molecule
- skeletal muscle