The dysregulation of lipid homeostasis is emerging as a hallmark of many CNS diseases. As aberrant protein regulation is suggested to be a shared pathological feature amongst many neurodegenerative conditions, such as Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD), disruptions in neuronal lipid processing may contribute to disease progression in the CNS. Specifically, given the endoplasmic reticulum (ER) dual role in lipid homeostasis as well as protein quality control (PQC) via unfolded protein response (UPR), lipid dysregulation in the CNS may converge on ER functioning and constitute a crucial mechanism underlying aberrant protein aggregation. In the current review, we discuss the diverse roles of lipid species as essential components of the CNS. Moreover, given the importance of both lipid dysregulation and protein aggregation in pathology of CNS diseases, we attempt to assess the potential downstream cross-talk between lipid dysregulation and ER dependent PQC mechanisms, with special focus on HIV-associated neurodegenerative disorders (HAND).

脂质稳态失调正在成为许多中枢神经系统疾病的标志。由于异常的蛋白质调节被认为是许多神经退行性疾病（例如阿尔茨海默病（AD）、帕金森病（PD）和亨廷顿病（HD））的共同病理特征，因此神经元脂质加工的破坏可能会导致疾病进展。中枢神经系统。具体而言，考虑到内质网（ER）在脂质稳态以及通过未折叠蛋白反应（UPR）进行蛋白质质量控​​制（PQC）中的双重作用，中枢神经系统中的脂质失调可能集中在ER功能上，并构成异常蛋白质聚集的关键机制。在当前的综述中，我们讨论了脂质种类作为中枢神经系统重要组成部分的不同作用。此外，考虑到脂质失调和蛋白质聚集在 CNS 疾病病理学中的重要性，我们尝试评估脂质失调和 ER 依赖性 PQC 机制之间潜在的下游串扰，特别关注 HIV 相关的神经退行性疾病 (HAND)。