Akyuz Enes, Arulsamy Alina, Aslan Feyza Sule, Sarisözen Bugra, Guney Beyzanur, Hekimoglu Abdulhekim, Yilmaz Beyza Nur, Retinasamy Thaarvena, Shaikh Mohd Farooq
Department of Biophysics, International School of Medicine, University of Health Sciences, Istanbul, Turkey.
Department of Pediatrics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
Mol Neurobiol. 2025 Feb;62(2):1631-1674. doi: 10.1007/s12035-024-04333-y. Epub 2024 Jul 16.
Alzheimer's disease (AD) is a progressive neurodegenerative disease. The accumulation of amyloid-β (Aβ) plaques and tau neurofibrillary tangles are the key players responsible for the pathogenesis of the disease. The accumulation of Aβ plaques and tau affect the balance in chemical neurotransmitters in the brain. Thus, the current review examined the role of neurotransmitters in the pathogenesis of Alzheimer's disease and discusses the alterations in the neurochemical activity and cross talk with their receptors and transporters. In the presence of Aβ plaques and neurofibrillary tangles, changes may occur in the expression of neuronal receptors which in turn triggers excessive release of glutamate into the synaptic cleft contributing to cell death and neuronal damage. The GABAergic system may also be affected by AD pathology in a similar way. In addition, decreased receptors in the cholinergic system and dysfunction in the dopamine neurotransmission of AD pathology may also contribute to the damage to cognitive function. Moreover, the presence of deficiencies in noradrenergic neurons within the locus coeruleus in AD suggests that noradrenergic stimulation could be useful in addressing its pathophysiology. The regulation of melatonin, known for its effectiveness in enhancing cognitive function and preventing Aβ accumulation, along with the involvement of the serotonergic system and histaminergic system in cognition and memory, becomes remarkable for promoting neurotransmission in AD. Additionally, nitric oxide and adenosine-based therapeutic approaches play a protective role in AD by preventing neuroinflammation. Overall, neurotransmitter-based therapeutic strategies emerge as pivotal for addressing neurotransmitter homeostasis and neurotransmission in the context of AD. This review discussed the potential for neurotransmitter-based drugs to be effective in slowing and correcting the neurodegenerative processes in AD by targeting the neurochemical imbalance in the brain. Therefore, neurotransmitter-based drugs could serve as a future therapeutic strategy to tackle AD.
阿尔茨海默病（AD）是一种进行性神经退行性疾病。淀粉样β（Aβ）斑块和tau神经原纤维缠结的积累是该疾病发病机制的关键因素。Aβ斑块和tau的积累会影响大脑中化学神经递质的平衡。因此，本综述研究了神经递质在阿尔茨海默病发病机制中的作用，并讨论了神经化学活性的改变以及它们与受体和转运体的相互作用。在存在Aβ斑块和神经原纤维缠结的情况下，神经元受体的表达可能会发生变化，进而触发谷氨酸过度释放到突触间隙，导致细胞死亡和神经元损伤。GABA能系统也可能以类似的方式受到AD病理的影响。此外，AD病理中胆碱能系统受体减少和多巴胺神经传递功能障碍也可能导致认知功能受损。而且，AD中蓝斑内去甲肾上腺素能神经元的缺陷表明，去甲肾上腺素能刺激可能有助于解决其病理生理学问题。褪黑素在增强认知功能和预防Aβ积累方面的有效性，以及血清素能系统和组胺能系统在认知和记忆中的作用，对于促进AD中的神经传递具有重要意义。此外，基于一氧化氮和腺苷的治疗方法通过预防神经炎症在AD中发挥保护作用。总体而言，基于神经递质的治疗策略对于解决AD背景下的神经递质稳态和神经传递至关重要。本综述讨论了基于神经递质的药物通过针对大脑中的神经化学失衡有效减缓并纠正AD神经退行性过程的潜力。因此，基于神经递质的药物可作为未来治疗AD的策略。
