Departments of Psychology, Veterinary and Comparative Anatomy, Pharmacology, and Physiology and Programs in Neuroscience and Biotechnology, Washington State University, P.O. Box 644820, Pullman, WA 99164-4820, USA.
Parkinsons Dis. 2012;2012:860923. doi: 10.1155/2012/860923. Epub 2012 Nov 7.
Parkinson's disease (PD) has become a major health problem affecting 1.5% of the world's population over 65 years of age. As life expectancy has increased so has the occurrence of PD. The primary direct consequence of this disease is the loss of dopaminergic (DA) neurons in the substantia nigra and striatum. As the intensity of motor dysfunction increases, the symptomatic triad of bradykinesia, tremors-at-rest, and rigidity occur. Progressive neurodegeneration may also impact non-DA neurotransmitter systems including cholinergic, noradrenergic, and serotonergic, often leading to the development of depression, sleep disturbances, dementia, and autonomic nervous system failure. L-DOPA is the most efficacious oral delivery treatment for controlling motor symptoms; however, this approach is ineffective regarding nonmotor symptoms. New treatment strategies are needed designed to provide neuroprotection and encourage neurogenesis and synaptogenesis to slow or reverse this disease process. The hepatocyte growth factor (HGF)/c-Met receptor system is a member of the growth factor family and has been shown to protect against degeneration of DA neurons in animal models. Recently, small angiotensin-based blood-brain barrier penetrant mimetics have been developed that activate this HGF/c-Met system. These compounds may offer a new and novel approach to the treatment of Parkinson's disease.
帕金森病（PD）已成为影响全球 65 岁以上人群 1.5%的主要健康问题。随着预期寿命的延长，PD 的发病率也有所增加。这种疾病的主要直接后果是黑质和纹状体中多巴胺能（DA）神经元的丧失。随着运动功能障碍的加剧，出现运动迟缓、静止性震颤和僵直的症状三联征。进行性神经退行性变还可能影响非 DA 神经递质系统，包括胆碱能、去甲肾上腺素能和血清素能系统，通常导致抑郁、睡眠障碍、痴呆和自主神经系统衰竭的发生。L-DOPA 是控制运动症状的最有效口服药物治疗方法；然而，对于非运动症状，这种方法无效。需要设计新的治疗策略，以提供神经保护作用，促进神经发生和突触形成，从而减缓或逆转这种疾病进程。肝细胞生长因子（HGF）/c-Met 受体系统是生长因子家族的一员，已被证明可防止动物模型中 DA 神经元的退化。最近，开发了基于血管紧张素的小血脑屏障穿透模拟物，可激活该 HGF/c-Met 系统。这些化合物可能为帕金森病的治疗提供一种新的方法。
