School of Pharmacy and Biomedical Science, University of Portsmouth, St. Michael's Building, White Sawn Road, Portsmouth, PO1 2DT, UK.
Adv Exp Med Biol. 2019;1175:325-333. doi: 10.1007/978-981-13-9913-8_12.
Oligodendrocytes form the myelin that ensheaths CNS axons, which is essential for rapid neuronal signalling and underpins the massive computing power of the human brain. Oligodendrocytes and myelin also provide metabolic and trophic support for axons and their disruption results in axonal demise and neurodegeneration, which are key features of Alzheimer's disease (AD). Notably, the brain has a remarkable capacity for regenerating oligodendrocytes, which is the function of adult oligodendrocyte progenitor cells (OPCs) or NG2-glia. White matter loss is often among the earliest brain changes in AD, preceding the tangles and plaques that characterize neuronal deficits. The underlying causes of myelin loss include oxidative stress, neuroinflammation and excitotoxicity, associated with accumulation of Aβ and tau hyperphosphorylation, pathological hallmarks of AD. Moreover, there is evidence that NG2-glia are disrupted in AD, which may be associated with disruption of synaptic signalling. This has led to the hypothesis that a vicious cycle of myelin loss and failure of regeneration from NG2-glia plays a key role in AD. Therapies that target NG2-glia are likely to have positive effects on myelination and neuroprotection in AD.
少突胶质细胞形成包裹中枢神经系统轴突的髓鞘，这对于快速的神经元信号传递至关重要，也是人类大脑巨大计算能力的基础。少突胶质细胞和髓鞘也为轴突提供代谢和营养支持，其功能障碍会导致轴突死亡和神经退行性变，这是阿尔茨海默病（AD）的关键特征。值得注意的是，大脑具有显著的再生少突胶质细胞的能力，这是成年少突胶质细胞前体细胞（OPCs）或 NG2 胶质细胞的功能。脑白质丢失通常是 AD 最早的大脑变化之一，早于神经元缺陷的缠结和斑块。髓鞘丢失的根本原因包括氧化应激、神经炎症和兴奋毒性，与 Aβ 和 tau 过度磷酸化的积累有关，这是 AD 的病理标志。此外，有证据表明，AD 中 NG2 胶质细胞受到破坏，这可能与突触信号传递的破坏有关。这导致了一个假设，即髓鞘丢失和 NG2 胶质细胞再生失败的恶性循环在 AD 中起着关键作用。针对 NG2 胶质细胞的治疗方法可能对 AD 中的髓鞘形成和神经保护具有积极影响。
