Neuronal cell death is the main pathological feature of chronic neurodegenerative diseases (NDs) such as Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). As age is strongly linked to NDs, these diseases are one of the leading medical and societal challenges faced by the rapidly aging western societies. Despite the increasing prevalence, the causes and mechanisms behind most NDs are still vague. A common hallmark of several NDs is the accumulation and aggregation of proteins. Prominent examples are amyloid beta and tau in Alzheimer’s disease, α−synuclein in Parkinson’s disease and transactive response DNA binding protein 43 kDa (TDP-43) in ALS and FTD. Under physiological conditions, protein quality control systems, namely the ubiquitin proteasome system and the autophagy machinery, eliminate such aberrant protein forms and thereby prevent proteotoxic stress. However, as proteins must unfold to undergo proteasomal degradation, aggregated proteins are poor substrates for the proteasome. Such proteins are thought to be primarily turned over by autophagy. Therefore, autophagy is considered a critical ND-protective pathway, which opens up potential new therapeutic interventions. One drawback is that the majority of research in NDs has been focused on elucidating the underlying pathomechanisms in neurons. However, neurons make up only about half of the brain cells with neuroglia being the other major central nervous system (CNS) cell type. Due to the ubiquitous presence of disease-causing mutations in all cells of the CNS, it is likely that non-neuronal cells contribute to the disease onset and/or progression. While our understanding of the roles of autophagy and its contribution to neurodegeneration in neurons deepened considerably over the last years, still comparatively little is known about the functions and disease contribution of the autophagy machinery in glia cells.

神经元细胞死亡是慢性神经退行性疾病（ND）的主要病理特征，例如阿尔茨海默氏病（AD），帕金森氏病（PD），肌萎缩性侧索硬化症（ALS）和额颞痴呆（FTD）。由于年龄与ND密切相关，因此这些疾病是西方迅速老龄化社会所面临的主要医学和社会挑战之一。尽管患病率不断上升，但大多数ND背后的原因和机制仍不明确。几种ND的共同特征是蛋白质的积累和聚集。突出的例子是阿尔茨海默氏病中的淀粉样蛋白β和tau，帕金森氏病中的α-突触核蛋白以及ALS和FTD中的反应活性DNA结合蛋白43 kDa（TDP-43）。在生理条件下，蛋白质质量控​​制系统，即泛素蛋白酶体系统和自噬机制，消除了这种异常的蛋白质形式，从而防止了蛋白毒性应激。但是，由于蛋白质必须展开才能经历蛋白酶体降解，因此聚集的蛋白质是蛋白酶体的不良底物。这种蛋白质被认为主要是通过自噬而被翻转的。因此，自噬被认为是重要的ND保护途径，这开辟了潜在的新治疗手段。一个缺点是，ND的大部分研究都集中在阐明神经元的潜在发病机制上。但是，神经元仅占大脑细胞的一半，而神经胶质细胞则是另一种主要的中枢神经系统（CNS）细胞类型。由于中枢神经系统所有细胞中普遍存在致病突变，非神经元细胞可能有助于疾病的发作和/或发展。近年来，虽然我们对自噬作用及其对神经元神经变性的贡献的理解已大大加深，但对自噬机制在神经胶质细胞中的功能和疾病贡献的了解仍然相对较少。