多巴胺与神经退行性疾病研究进展

多巴胺调控人类的情绪和认识能力,包括思想、感觉、理解、推理等,同时,它也在人类的运动功能中发挥重要作用。研究表明多巴胺的合成、储存、释放、降解和重摄取等失衡均与中枢神经系统的多种退行性疾病有密切联系,同时许多治疗疾病的有效药物也围绕多巴胺的研究而产生,如多巴胺替代疗法改善帕金森病的运动症状,多巴胺受体阻断剂可改善舞蹈病的运动症状以及调节多种疾病的精神症状,在临床上都取得了可喜的疗效。然而目前未发现与多巴胺代谢直接相关的基因突变,因此未来需要继续深入研究在神经退行性疾病中造成多巴胺代谢失常的机制,旨在为临床新药物靶点和新治疗手段的研发提供线索。

Research progress of dopamine in neurodegenerative diseases

Dopamine is known to regulate human emotions and cognitive abilities, including thinking, feeling, understanding, reasoning, etc. It also plays an important role in motor fimction. Studies reveal a close relationship between neurodegenerative diseases of the central nervous system and imbalance in dopamine synthesis, storage, release, degradation and reuptake. Furthermore, drugs targeting dopamine system have achieved encouraging efficacy clinically, e.g., dopamine replacement therapy improves motor symptoms of Parkinson＇s disease patients; dopamine receptor antagonist ameliorates motor symptoms of Huntington＇s disease patients and modulates a variety of psychiatric symptoms of different diseases. Here, we review the current understanding of dopamine function in 7 neurodegenerative diseases, including Parkinson＇s disease, Huntington＇s Disease, Amyotrophic Lateral Sclerosis, Alzheimer＇s Disease, Frontotemporal Dementia, Multiple Sclerosis, and Prion Disease. Surprisingly, no gene mutation is detected in dopamine metabolism in these diseases. Future mechanistic studies on involvement of dopamine metabolism in neurodegenerative diseases will shed light on clinical drug development and novel alternative therapies.