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Recent Advances in Neurogenic Small Molecules as Innovative Treatments for Neurodegenerative Diseases

机译:神经源性小分子作为神经退行性疾病的创新疗法的最新进展

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摘要

The central nervous system of adult mammals has long been considered as a complex static structure unable to undergo any regenerative process to refurbish its dead nodes. This dogma was challenged by Altman in the 1960s and neuron self-renewal has been demonstrated ever since in many species, including humans. Aging, neurodegenerative, and some mental diseases are associated with an exponential decrease in brain neurogenesis. Therefore, the controlled pharmacological stimulation of the endogenous neural stem cells (NSCs) niches might counteract the neuronal loss in Alzheimer’s disease (AD) and other pathologies, opening an exciting new therapeutic avenue. In the last years, druggable molecular targets and signalling pathways involved in neurogenic processes have been identified, and as a consequence, different drug types have been developed and tested in neuronal plasticity. This review focuses on recent advances in neurogenic agents acting at serotonin and/or melatonin systems, Wnt/β-catenin pathway, sigma receptors, nicotinamide phosphoribosyltransferase (NAMPT) and nuclear erythroid 2-related factor (Nrf2).
机译:长期以来,成年哺乳动物的中枢神经系统被认为是一种复杂的静态结构,无法经历任何再生过程来修复其死结。这种教条在1960年代受到Altman的挑战,从那以后,包括人类在内的许多物种都表现出了神经元自我更新。衰老,神经退行性疾病和某些精神疾病与脑神经发生指数下降有关。因此,对内源性神经干细胞(NSC)壁the的可控药理刺激可能会抵消阿尔茨海默氏病(AD)和其他疾病的神经元丢失,从而开辟了令人兴奋的新治疗途径。近年来,已经确定了涉及神经发生过程的可药物分子靶标和信号传导途径,因此,已经开发了不同的药物类型并在神经元可塑性方面进行了测试。这篇综述着重于神经元药物在5-羟色胺和/或褪黑素系统,Wnt /β-catenin途径,sigma受体,烟酰胺磷酸核糖基转移酶(NAMPT)和核红系2相关因子(Nrf2)方面的最新进展。

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