Farzanehfar Parisa
Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, 3010, Australia.
St Vincent's Hospital, Fitzroy, Victoria, 3065, Australia.
Neurochem Res. 2016 Dec;41(12):3161-3170. doi: 10.1007/s11064-016-2053-3. Epub 2016 Sep 10.
The motor symptoms of Parkinson's disease (PD) are caused by degeneration of dopamine (DA) neurons in the substantia nigra pars compacta (SNc) of midbrain. Given the fact that current treatment options are mostly symptomatic and based on increasing DA level in the nigrostriatal system, it is generally believed the most effective and long-lasting treatment for PD motor symptoms will be replacing SNc DA cells, either by endogenous repair (i.e. neurogenesis) or cell transplantation. While cell transplantation is hindered by failure of acquisition and maintenance of the DA phenotype by transplanted cells, hope rests upon non-invasive cell replacement therapy (CRT) with endogenous neural stem cells, which have the potential to give rise to new neurons including DA neurons. Understanding underlying mechanisms and signalling pathways of neurogenesis in the adult brain could shed light on obstacles to achieve effective CRTs and better treatments for PD. This paper first reviews different therapeutic strategies in context of PD along with their advantages and disadvantages followed by an extensive review of adult neurogenesis.
帕金森病(PD)的运动症状是由中脑黑质致密部(SNc)多巴胺(DA)神经元变性所致。鉴于目前的治疗选择大多是对症治疗,且基于提高黑质纹状体系统中的DA水平,人们普遍认为,对PD运动症状最有效且持久的治疗方法是通过内源性修复(即神经发生)或细胞移植来替代SNc DA细胞。虽然细胞移植因移植细胞难以获得并维持DA表型而受到阻碍,但人们寄希望于利用内源性神经干细胞进行非侵入性细胞替代疗法(CRT),因为这些干细胞有可能产生包括DA神经元在内的新神经元。了解成人大脑中神经发生的潜在机制和信号通路,有助于揭示实现有效CRT以及更好治疗PD的障碍。本文首先回顾了PD背景下的不同治疗策略及其优缺点,随后对成体神经发生进行了广泛综述。