PPARα途径治疗阿尔兹海默症研究进展

New Progress of PPARαPathway in Alzheimer's Disease

过氧化物酶体增殖物激活受体α(PPARα)属于配体调节核受体(PPAR)家族。PPARα参与编码与谷氨酸稳态和脑胆碱能/多巴胺能信号传导有关蛋白质基因的调控。另外,PPARα调节编码淀粉样前体蛋白(APP)代谢中涉及酶基因的表达。它激活编码α分泌酶的基因,该基因负责APP降解的非淀粉样蛋白产生途径。它还下调β分泌酶(BACE-1),这是在阿尔茨海默氏病(AD)中释放淀粉样β的主要酶。PPARα是一种转录因子,可调节参与脂肪酸代谢的基因并激活肝脏自噬。PPARα的下调可能减少抗氧化剂和抗炎过程,这可能与AD患者大脑中的脂肪酸转运,脂质代谢和线粒体功能障碍有关。因此,PPARα的特定激活剂对于改善神经变性和神经发育障碍中的脑细胞代谢和认知功能可能很重要。

Peroxisome proliferator activated receptorα(PPARα)belongs to the ligand regulated nuclear receptor(PPAR)family.PPARαis involved in the regulation of genes encoding proteins related to glutamate homeostasis and brain cholinergic/dopaminergic signaling.In addition,PPARαregulates the expression of genes encoding enzymes involved in the metabolism of amyloid precursor protein(APP).It activates the gene encoding alpha secretase,which is responsible for the production of non-amyloid protein degraded by amyloid precursor protein.It also downregulatesβ-secretase(BACE-1),the main enzyme that releases amyloidβin Alzheimer's disease(AD).PPARαis a transcription factor that regulates genes involved in fatty acid metabolism and activates liver autophagy.The down-regulation of PPARαmay reduce the antioxidant and anti-inflammatory processes,which may be related to the brain fatty acid transport,lipid metabolism and mitochondrial dysfunction in AD patients.Therefore,PPARαspecific activators may be important for improving brain cell metabolism and cognitive function in neurodegenerative and neurodevelopmental disorders.