Center for Neurogastroenterology, Division of Gastroenterology and Hepatology, Department of Medicine.
Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering.
J Clin Invest. 2021 Jul 1;131(13). doi: 10.1172/JCI143775.
Neurodegenerative disorders (NDs) affect essential functions not only in the CNS, but also cause persistent gut dysfunctions, suggesting that they have an impact on both CNS and gut-innervating neurons. Although the CNS biology of NDs continues to be well studied, how gut-innervating neurons, including those that connect the gut to the brain, are affected by or involved in the etiology of these debilitating and progressive disorders has been understudied. Studies in recent years have shown how CNS and gut biology, aided by the gut-brain connecting neurons, modulate each other's functions. These studies underscore the importance of exploring the gut-innervating and gut-brain connecting neurons of the CNS and gut function in health, as well as the etiology and progression of dysfunction in NDs. In this Review, we discuss our current understanding of how the various gut-innervating neurons and gut physiology are involved in the etiology of NDs, including Parkinson's disease, Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis, to cause progressive CNS and persistent gut dysfunction.
神经退行性疾病(NDs)不仅影响中枢神经系统(CNS)的基本功能,还会导致持续的肠道功能障碍,这表明它们对 CNS 和支配肠道的神经元都有影响。尽管 NDs 的中枢神经系统生物学仍在被深入研究,但支配肠道的神经元(包括将肠道与大脑连接起来的神经元)如何受到这些使人衰弱和进行性疾病的影响或参与其发病机制,这方面的研究还很不足。近年来的研究表明,中枢神经系统和肠道生物学在连接肠道和大脑的神经元的辅助下,如何相互调节彼此的功能。这些研究强调了探索中枢神经系统和肠道的支配肠道的和连接肠道与大脑的神经元以及肠道功能在健康状态下以及在 NDs 中功能障碍的发病和进展中的重要性。在这篇综述中,我们讨论了我们目前对各种支配肠道的神经元和肠道生理学如何参与 NDs(包括帕金森病、阿尔茨海默病、亨廷顿病和肌萎缩侧索硬化症)发病机制的理解,这些疾病会导致进行性 CNS 和持续的肠道功能障碍。