The discovery of transcription factor EB (TFEB) as a master regulator of the autophagy–lysosomal pathway (ALP) has triggered increasing numbers of studies that aim to explore the therapeutic potential of targeting TFEB to treat neurodegenerative disorders (NDs) such as Alzheimer’s disease and Parkinson’s disease. So far, the findings are exciting and promising. Here, we delineate the dysfunction of the TFEB-mediated ALP in NDs, and we summarize small molecules that have been identified as TFEB activators, along with their protective effects in NDs. We discuss the molecular mechanisms and targets, and the pros and cons of these TFEB activators from the perspective of drug development. Specific and potent small-molecule TFEB activators with ideal brain bioavailability could provide a method for treating NDs.

转录因子 EB (TFEB) 作为自噬-溶酶体途径 (ALP) 的主要调节因子的发现引发了越来越多的研究，旨在探索靶向 TFEB 治疗神经退行性疾病 (ND) 的治疗潜力，例如阿尔茨海默病和帕金森病。到目前为止，这些发现是令人兴奋和有希望的。在这里，我们描述了 NDs 中 TFEB 介导的 ALP 的功能障碍，并总结了已被鉴定为 TFEB 激活剂的小分子，以及它们在 NDs 中的保护作用。我们从药物开发的角度讨论了这些 TFEB 激活剂的分子机制和靶点，以及利弊。具有理想大脑生物利用度的特异性强效小分子 TFEB 激活剂可以提供一种治疗 NDs 的方法。