Mather Mara
Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA.
Department of Psychology, University of Southern California, Los Angeles, CA, USA.
Nat Rev Neurosci. 2025 May;26(5):276-292. doi: 10.1038/s41583-025-00911-8. Epub 2025 Mar 26.
In addition to their more studied cognitive and motor effects, neurodegenerative diseases are also associated with impairments in autonomic function - the regulation of involuntary physiological processes. These autonomic impairments manifest in different ways and at different stages depending on the specific disease. The neural networks responsible for autonomic regulation in the brain and body have characteristics that render them particularly susceptible to the prion-like spread of protein aggregation involved in neurodegenerative diseases. Specifically, the axons of these neurons - in both peripheral and central networks - are long and poorly myelinated axons, which make them preferential targets for pathological protein aggregation. Moreover, cortical regions integrating information about the internal state of the body are highly connected with other brain regions, which increases the likelihood of intersection with pathological pathways and prion-like spread of abnormal proteins. This leads to an autonomic 'signature' of dysfunction, characteristic of each neurodegenerative disease, that is linked to the affected networks and regions undergoing pathological aggregation.
除了其更为人所研究的认知和运动影响外，神经退行性疾病还与自主神经功能障碍有关——自主神经功能是对非自主生理过程的调节。这些自主神经障碍根据具体疾病以不同方式和在不同阶段表现出来。负责大脑和身体自主神经调节的神经网络具有一些特征，使其特别容易受到神经退行性疾病中涉及的蛋白质聚集的朊病毒样传播的影响。具体而言，这些神经元的轴突——在外周和中枢网络中——都是长且髓鞘形成不良的轴突，这使它们成为病理性蛋白质聚集的优先靶点。此外，整合有关身体内部状态信息的皮质区域与其他脑区高度相连，这增加了与病理途径相交以及异常蛋白质朊病毒样传播的可能性。这导致了功能障碍的自主神经“特征”，这是每种神经退行性疾病的特征，与经历病理聚集的受影响网络和区域相关联。
