Role and research progress of CYP46A1 in neurodegenerative diseases / 中国临床药理学与治疗学

Cytochrome P450 (CYP46A1) is a central neuro-specific metabolic enzyme that converts cholesterol into 24-hydroxycholesterol. This metabolic process is the main mechanism of cholesterol elimination in brain and is closely related to the occurrence and development of neurodegenerative diseases. This review focuses on the relationship between CYP46A1 and neurodegenerative diseases, from the aspects of regulatory mechanism of CYP46A1 enzyme, the relationship between CYP46A1 and cognitive dysfunction, epileptic encephalopathy, and CYP46A1 enzyme activity modifiers (inhibitors and agonists) to illustrate the pivotal role of CYP46A1 in the development and prevention of neurodegenerative diseases in hope of providing new target and direction for the research and development of new drugs.

Overexpression of CYP46A1 has anti-Alzheimer's disease like effects / 解放军医学杂志

Objective To investigate the effect of CYP46A1 on the pathogenesis of Alzheimer's disease.Methods Recombinant lentiviral vectors which including anthropogenic CYP46A1 were injected into bilateral hippocampus of 3-monthold male 5XFAD transgenic mice,while empty vectors were injected into the corresponding position of the control group.After two months,the ability of learning and memory were tested by Morris water maze and T maze experiments,and amyloid plaque and inflammatory infiltration in the brain were detected by immunohistochemical staining and ELISA respectively.Results Compared with the control group,CYP46A1 virus injection significantly increased the CYP46A1 mRNA and protein expression in hippocampus.In addition,CYP46A1 overexpression significantly decreased the latency to find the platform in Morris water maze test and increased the correct rate to choose in T maze test.Aβ immunohistochemical staining and plaques area statistics demonstrated that the amyloid plaque area of hippocampus in CYP46A1 overexpression mice was significantly reduced,and there was a significantly decrease of hippocampal astrocytes expression by means of GFAP staining.Furthermore,hippocampal CYP46A1 overexpression significantly decreased the expression level of Aβ40,Aβ42,IL-1β and TNF-α,while compare with the control group.Conclusion CYP46A1 overexpression in hippocampus can promote the cognitive impairment,as well as ameliorate the brain inflammatory infiltration in 5XFAD transgenic mice,suggesting that CYP46A1 has anti-Alzheimer's disease like effects.