PDF(Pubmed)
Abstract：
Peroxisome proliferator-activated receptors (PPARs) may play an important role in the pathomechanism/pathogenesis of Alzheimer\'s disease (AD) and several other neurological/neuropsychiatric disorders. AD leads to progressive alterations in the redox state, ion homeostasis, lipids, and protein metabolism. Significant alterations in molecular processes and the functioning of several signaling pathways result in the degeneration and death of synapses and neuronal cells, leading to the most severe dementia. Peroxisome proliferator-activated receptor alpha (PPAR-α) is among the processes affected by AD; it regulates the transcription of genes related to the metabolism of cholesterol, fatty acids, other lipids and neurotransmission, mitochondria biogenesis, and function. PPAR-α is involved in the cholesterol transport to mitochondria, the substrate for neurosteroid biosynthesis. PPAR-α-coding enzymes, such as sulfotransferases, which are responsible for neurosteroid sulfation. The relation between PPAR-α and cholesterol/neurosteroids may have a significant impact on the course and progression of neurodegeneration/neuroprotection processes. Unfortunately, despite many years of intensive studies, the pathogenesis of AD is unknown and therapy for AD and other neurodegenerative diseases is symptomatic, presenting a significant goal and challenge today. This review presents recent achievements in therapeutic approaches for AD, which are targeting PPAR-α and its relation to cholesterol and neurosteroids in AD and neuropsychiatric disorders.
摘要：
过氧化物酶体增殖物激活受体(PPARs)可能在阿尔茨海默病(AD)和其他几种神经/神经精神疾病的发病机制中发挥重要作用。AD导致氧化还原状态的进行性改变，离子稳态，脂质，和蛋白质代谢。分子过程的显著改变和几个信号通路的功能导致突触和神经元细胞的变性和死亡,导致最严重的痴呆.过氧化物酶体增殖物激活受体α（PPAR-α）是受AD影响的过程之一；它调节与胆固醇代谢相关的基因的转录，脂肪酸，其他脂质和神经传递，线粒体生物发生，和功能。PPAR-α参与胆固醇向线粒体的转运，神经类固醇生物合成的底物。PPAR-α编码酶,如磺基转移酶，负责神经类固醇硫酸化。PPAR-α与胆固醇/神经类固醇之间的关系可能对神经变性/神经保护过程的过程和进展具有重大影响。不幸的是,尽管经过多年的深入研究，AD的发病机制尚不清楚，AD和其他神经退行性疾病的治疗是有症状的，今天提出了一个重要的目标和挑战。这篇综述介绍了AD治疗方法的最新进展。在AD和神经精神疾病中靶向PPAR-α及其与胆固醇和神经类固醇的关系。
