Novel Insight into Functions of Transcription Factor EB (TFEB) in Alzheimer’s Disease and Parkinson’s Disease

Jing Yang, Wei Zhang, Shugeng Zhang, Ashok Iyaswamy, Jichao Sun*, Jigang Wang*, Chuanbin Yang*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review


A key pathological feature of neurodegenerative diseases (NDs) such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) is the accumulation of aggregated and misfolded protein aggregates with limited effective therapeutic agents. TFEB (transcription factor EB), a key regulator of lysosomal biogenesis and autophagy, plays a pivotal role in the degradation of protein aggregates and has thus been regarded as a promising therapeutic target for these NDs. Here, we systematically summarize the molecular mechanisms and function of TFEB regulation. We then discuss the roles of TFEB and autophagy-lysosome pathways in major neurodegenerative diseases including AD and PD. Finally, we illustrate small molecule TFEB activators with protective roles in NDs animal models, which show great potential for being further developed into novel anti-neurodegenerative agents. Overall, targeting TFEB for enhancing lysosomal biogenesis and autophagy may represent a promising opportunity for the discovery of disease-modifying therapeutics for neurodegenerative disorders though more in-depth basic and clinical studies are required in the future.
Original languageEnglish
Number of pages18
JournalAging and Disease
Publication statusPublished - 3 Dec 2022

User-Defined Keywords

  • TFEB (transcription factor EB)
  • lysosome
  • autophagy
  • neurodegenerative disease
  • Alzheimer’s disease
  • Parkinson’s disease


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