Neuroscience Research Australia, Sydney, Australia.
Mov Disord. 2011 Jan;26(1):6-17. doi: 10.1002/mds.23455.
Glia are traditionally known as support cells for neurons, and their role in neurodegeneration has been largely considered secondary to neuronal dysfunction. We review newer concepts on glial function and assess glial changes in Parkinson's disease (PD) at the time of disease initiation when α-synuclein is accumulating in brain tissue but there is limited neuronal loss, and also as the disease progresses and neuronal loss is evident.
Of the two main types of astrocytes, only protoplasmic astrocytes are involved in PD, where they become nonreactive and accumulate α-synuclein. Experimental evidence has shown that astrocytic α-synuclein deposition initiates the noncell autonomous killing of neurons through microglial signaling. As the disease progresses, more protoplasmic astrocytes are affected by the disease with an increasing microglial response. Although there is still controversy on the role microglia play in neurodegeneration, there is evidence that microglia are activated early in PD and possibly assist with the clearance of extracellular α-synuclein at this time. Microglia transform to phagocytes and target neurons as the disease progresses but appear to become dysfunctional with increasing amounts of ingested debris. Only nonmyelinating oligodendroglial cells are affected in PD, and only late in the disease process.
Glial cells are responsible for the progression of PD and play an important role in initiating the early tissue response. In particular, early dysfunction and α-synuclein accumulation in astrocytes causes recruitment of phagocytic microglia that attack selected neurons in restricted brain regions causing the clinical symptoms of PD.
神经胶质细胞传统上被认为是神经元的支持细胞，其在神经退行性变中的作用在很大程度上被认为次于神经元功能障碍。我们综述了神经胶质细胞功能的新概念，并评估了在帕金森病（PD）发病时（当α-突触核蛋白在脑组织中积累但神经元丢失有限时）以及随着疾病进展和神经元丢失明显时的神经胶质变化。
在两种主要类型的星形胶质细胞中，只有原浆型星形胶质细胞参与 PD，在 PD 中它们变得非反应性并积累α-突触核蛋白。实验证据表明，星形胶质细胞α-突触核蛋白沉积通过小胶质细胞信号引发非细胞自主的神经元杀伤。随着疾病的进展，更多的原浆型星形胶质细胞受到疾病的影响，小胶质细胞的反应也随之增加。尽管小胶质细胞在神经退行性变中的作用仍存在争议，但有证据表明小胶质细胞在 PD 早期被激活，并且可能在此时间协助清除细胞外α-突触核蛋白。小胶质细胞随着疾病的进展转变为吞噬细胞并靶向神经元，但随着摄入的碎片越来越多，它们似乎变得功能失调。只有非髓鞘形成的少突胶质细胞在 PD 中受到影响，而且仅在疾病后期。
神经胶质细胞是 PD 进展的罪魁祸首，在引发早期组织反应中发挥着重要作用。特别是星形胶质细胞的早期功能障碍和α-突触核蛋白积累会招募吞噬性小胶质细胞，这些小胶质细胞攻击特定脑区的选定神经元，导致 PD 的临床症状。
