van Neerven Sabien, Kampmann Eric, Mey Jörg
Institute of Biology II, RWTH Aachen, Aachen, Germany.
Prog Neurobiol. 2008 Aug;85(4):433-51. doi: 10.1016/j.pneurobio.2008.04.006. Epub 2008 May 4.
Retinoids are important signals in brain development. They regulate gene transcription by binding to retinoic acid receptors (RAR) and, as was discovered recently, a peroxisome proliferator-activated receptor (PPAR). Traditional ligands of PPAR are best known for their functions in lipid metabolism and inflammation. RAR and PPAR are ligand-activated transcription factors, which share members of the retinoid X receptor (RXR) family as heterodimeric partners. Both signal transduction pathways have recently been implicated in the progression of neurodegenerative and psychiatric diseases. Since inflammatory processes contribute to various neurodegenerative diseases, the anti-inflammatory activity of retinoids and PPARgamma agonists recommends them as potential therapeutic targets. In addition, genetic linkage studies, transgenic mouse models and experiments with vitamin A deprivation provide evidence that retinoic acid signaling is directly involved in physiology and pathology of motoneurons, of the basal ganglia and of cognitive functions. The activation of PPAR/RXR and RAR/RXR transcription factors has therefore been proposed as a therapeutic strategy in disorders of the central nervous system.
维甲酸是大脑发育中的重要信号。它们通过与视黄酸受体（RAR）结合来调节基因转录，并且最近发现，还可与过氧化物酶体增殖物激活受体（PPAR）结合。PPAR的传统配体以其在脂质代谢和炎症中的功能而闻名。RAR和PPAR是配体激活的转录因子，它们以类视黄醇X受体（RXR）家族成员作为异二聚体伴侣。最近发现这两种信号转导途径都与神经退行性疾病和精神疾病的进展有关。由于炎症过程会导致各种神经退行性疾病，维甲酸和PPARγ激动剂的抗炎活性使其成为潜在的治疗靶点。此外，基因连锁研究、转基因小鼠模型以及维生素A缺乏实验提供了证据，表明视黄酸信号直接参与运动神经元、基底神经节的生理和病理过程以及认知功能。因此，PPAR/RXR和RAR/RXR转录因子的激活已被提议作为中枢神经系统疾病的一种治疗策略。
