感染在神经退行性疾病中的调控机制

Regulatory mechanisms of infection in neurodegenerative diseases

摘要:

神经退行性疾病以突触丢失和神经元死亡为特征，表现为认知功能下降、痴呆和运动功能丧失。流行病学和实验证据提示：慢性细菌、病毒和真菌感染可能是导致神经退行性疾病如阿尔兹海默症（AD）、帕金森病（PD）、肌萎缩性侧索硬化症（ALS）和多发性硬化症（MS）等的危险因素。病原体在中枢神经系统的持续感染可导致一系列细胞生物学功能的异常，如诱导蛋白质的错误折叠和聚集、导致氧化应激损伤、细胞自噬异常以及神经元凋亡和坏死等；感染还会触发炎症介质释放并激活宿主免疫应答；此外，感染还可引起慢性神经炎症并导致能量代谢障碍等。本文就感染在神经退行性疾病中的作用机制及其研究进展作一综述，从而为科研人员开发新的药物和治疗方法提供新思路。

Abstract:

Neurodegenerative diseases are generally characterized by loss of synapses and death of neurons, leading to decreased cognitive function, dementia and loss of motor function. Increasing epidemiological and experimental evidence indicates that chronic bacterial, viral and fungal infections may cause neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis and Multiple sclerosis. Chronic infections in the central nervous system could lead to a series of cellular disfunction such as protein misfolding and aggregation, increased oxidative stress, abnormal autophagy, neuronal apoptosis or necrosis. Pathogen infection may also trigger the release of inflammatory mediators and the activation of host immune responses. Furthermore, infection could lead to chronic nerve inflammation and metabolic dysfunction. Here we review recent progress in the research of the regulatory roles and mechanisms of infections in the pathogenesis of neurodegenerative diseases. A better understanding of the relationship between pathogenic infections and neurodegenerative diseases will promote the development of new drugs and therapies.