Department of Drug Discovery and Biomedical Sciences, College of Pharmacy, University of South Carolina, 715 Sumter Street, Columbia, SC 29208, USA.
Int J Mol Sci. 2023 Oct 19;24(20):15340. doi: 10.3390/ijms242015340.
Neurodegenerative diseases affect millions of people worldwide. Neurodegenerative diseases result from progressive damage to nerve cells in the brain or peripheral nervous system connections that are essential for cognition, coordination, strength, sensation, and mobility. Dysfunction of these brain and nerve functions is associated with Alzheimer's disease, Parkinson's disease, Huntington's disease, Amyotrophic lateral sclerosis, and motor neuron disease. In addition to these, 50% of people living with HIV develop a spectrum of cognitive, motor, and/or mood problems collectively referred to as HIV-Associated Neurocognitive Disorders (HAND) despite the widespread use of a combination of antiretroviral therapies. Neuroinflammation and neurotransmitter systems have a pathological correlation and play a critical role in developing neurodegenerative diseases. Each of these diseases has a unique pattern of dysregulation of the neurotransmitter system, which has been attributed to different forms of cell-specific neuronal loss. In this review, we will focus on a discussion of the regulation of dopaminergic and cholinergic systems, which are more commonly disturbed in neurodegenerative disorders. Additionally, we will provide evidence for the hypothesis that disturbances in neurotransmission contribute to the neuronal loss observed in neurodegenerative disorders. Further, we will highlight the critical role of dopamine as a mediator of neuronal injury and loss in the context of NeuroHIV. This review will highlight the need to further investigate neurotransmission systems for their role in the etiology of neurodegenerative disorders.
神经退行性疾病影响着全球数百万人。神经退行性疾病是由于大脑或外周神经系统连接的神经细胞进行性损伤引起的，这些神经细胞对于认知、协调、力量、感觉和运动至关重要。这些大脑和神经功能的功能障碍与阿尔茨海默病、帕金森病、亨廷顿病、肌萎缩侧索硬化症和运动神经元病有关。此外，尽管广泛使用了抗逆转录病毒疗法的联合治疗，但仍有 50%的艾滋病毒感染者会出现一系列认知、运动和/或情绪问题，统称为与艾滋病毒相关的神经认知障碍 (HAND)。神经炎症和神经递质系统具有病理相关性，在神经退行性疾病的发展中起着关键作用。这些疾病中的每一种都有其独特的神经递质系统失调模式，这归因于不同形式的特定于细胞的神经元丧失。在这篇综述中，我们将重点讨论多巴胺能和胆碱能系统的调节，这两种系统在神经退行性疾病中更为常见。此外，我们将提供证据支持这样一种假设，即神经传递的紊乱导致了神经退行性疾病中观察到的神经元丧失。此外，我们将强调多巴胺作为神经损伤和神经元丧失的中介物在神经 HIV 中的关键作用。这篇综述强调了需要进一步研究神经传递系统在神经退行性疾病病因学中的作用。
