Peroxisome proliferator activated receptor alpha (PPAR-α) belongs to the family of ligand-regulated nuclear receptors (PPARs). These receptors after heterodimerization with retinoid X receptor (RXR) bind in promotor of target genes to PPAR response elements (PPREs) and act as a potent transcription factors. PPAR-α and other receptors from this family, such as PPAR-β/δ and PPAR-γ are expressed in the brain and other organs and play a significant role in oxidative stress, energy homeostasis, mitochondrial fatty acids metabolism and inflammation. PPAR-α takes part in regulation of genes coding proteins that are involved in glutamate homeostasis and cholinergic/dopaminergic signaling in the brain. Moreover, PPAR-α regulates expression of genes coding enzymes engaged in amyloid precursor protein (APP) metabolism. It activates gene coding of α secretase, which is responsible for non-amyloidogenic pathway of APP degradation. It also down regulates β secretase (BACE-1), the main enzyme responsible for amyloid beta (Aβ) peptide release in Alzheimer Diseases (AD). In AD brain expression of genes of PPAR-α and PPAR-γ coactivator-1 alpha (PGC-1α) is significantly decreased. PPARs are altered not only in AD but in other neurodegenerative/neurodevelopmental and psychiatric disorder. PPAR-α downregulation may decrease anti-oxidative and anti-inflammatory processes and could be responsible for the alteration of fatty acid transport, lipid metabolism and disturbances of mitochondria function in the brain of AD patients. Specific activators of PPAR-α may be important for improvement of brain cells metabolism and cognitive function in neurodegenerative and neurodevelopmental disorders.

中文翻译：

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PPARα在脑中的新作用：阿尔茨海默氏病和其他神经退行性疾病的治疗中有望的目标。

过氧化物酶体增殖物激活受体α（PPAR-α）属于配体调节核受体（PPAR）家族。这些与类视黄醇X受体（RXR）异源二聚化后的受体在靶基因的启动子上与PPAR反应元件（PPRE）结合并充当有效的转录因子。PPAR-α和该家族的其他受体（例如PPAR-β/δ和PPAR-γ）在大脑和其他器官中表达，并且在氧化应激，能量稳态，线粒体脂肪酸代谢和炎症中起重要作用。PPAR-α参与基因编码蛋白的调控，这些蛋白与谷氨酸稳态和大脑胆碱能/多巴胺能信号传导有关。此外，PPAR-α调节编码参与淀粉样前体蛋白（APP）代谢的酶的基因的表达。它激活α分泌酶的基因编码，这负责APP降解的非淀粉样生成途径。它也下调β分泌酶（BACE-1），这是负责阿尔茨海默病（AD）中淀粉样β（Aβ）肽释放的主要酶。在AD大脑中，PPAR-α和PPAR-γcoactivator-1α（PGC-1α）基因的表达显着降低。PPARs不仅在AD中发生改变，而且在其他神经退行性/神经发育和精神疾病中也发生改变。PPAR-α的下调可能会降低抗氧化和抗炎过程，并可能导致AD患者大脑中脂肪酸转运，脂质代谢和线粒体功能的改变。PPAR-α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。