Electroacupuncture ameliorates beta-amyloid pathology and cognitive impairment in Alzheimer disease via a novel mechanism involving activation of TFEB (transcription factor EB)

Xiaoyan Zheng, Wenjia Lin, Yimin Jiang, Kejia Lu, Wenjing Wei, Qingwei Huo, Shaoyang Cui, Xifei Yang, Min Li, Nenggui Xu, Chunzhi Tang, Ju Xian Song*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Alzheimer disease (AD) is the most prevalent neurodegenerative disorder leading to dementia in the elderly. Unfortunately, no cure for AD is available to date. Increasing evidence has proved the roles of misfolded protein aggregation due to impairment of the macroautophagy/autophagy-lysosomal pathway (ALP) in the pathogenesis of AD, and thus making TFEB (transcription factor EB), which orchestrates ALP, as a promising target for treating AD. As a complementary therapy, acupuncture or electroacupuncture (EA) has been commonly used for treating human diseases. Although the beneficial effects of acupuncture for AD have been primarily studied both pre-clinically and clinically, the real efficacy of acupuncture on AD remains inconclusive and the underlying mechanisms are largely unexplored. In this study, we demonstrated the cognitive-enhancing effect of three-needle EA (TNEA) in an animal model of AD with beta-amyloid (Aβ) pathology (5xFAD). TNEA reduced APP (amyloid beta (A4) precursor protein), C-terminal fragments (CTFs) of APP and Aβ load, and inhibited glial cell activation in the prefrontal cortex and hippocampus of 5xFAD. Mechanistically, TNEA activated TFEB via inhibiting the AKT-MAPK1-MTORC1 pathway, thus promoting ALP in the brains. Therefore, TNEA represents a promising acupuncture therapy for AD, via a novel mechanism involving TFEB activation.


Original languageEnglish
Pages (from-to)3833-3847
Number of pages15
JournalAutophagy
Volume17
Issue number11
DOIs
Publication statusPublished - 2 Nov 2021

Scopus Subject Areas

  • Molecular Biology
  • Cell Biology

User-Defined Keywords

  • Alzheimer disease
  • autophagy-lysosomal pathway
  • electroacupuncture
  • transcription factor EB

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