Presenilin-1 regulates the expression of p62 to govern p62-dependent tau degradation

Ying Tsen Tung, Bo Jeng Wang, Wen Ming Hsu, Ming Kuan Hu, Guor Mour Her, Wei Pang Huang*, Yung Feng Liao

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

8 Scopus citations


Mutations in presenilin-1 (PS1) are tightly associated with early-onset familial Alzheimer's disease (FAD), which is characterized by extracellular amyloid plaques and the accumulation of intracellular Tau. In addition to being the catalytic subunit of γ-secretase, PS1 has been shown to regulate diverse cellular functions independent of its proteolytic activity. We found that cells deficient in PS1 exhibit reduced levels of p62 protein, a cargo-receptor shuttling Tau for degradation. The downregulation of PS1 led to a significant decrease in both the protein and mRNA transcript of p62, concomitant with attenuated p62 promoter activity. This PS1-dependent regulation of p62 expression was mediated through an Akt/AP-1 pathway independent of the proteolytic activity of PS1/γ-secretase. This p62-mediated Tau degradation was significantly impaired in PS1-deficient cells, which can be rescued by ectopic expression of either p62 or wild-type PS1 but not mutant PS1 containing FAD-linked mutations. Our study suggests a novel function for PS1 in modulating p62 expression to control the proteostasis of Tau.

Original languageEnglish
Pages (from-to)10-27
Number of pages18
JournalMolecular Neurobiology
Issue number1
StatePublished - Feb 2014


  • Alzheimer's disease
  • Autophagy
  • p62
  • Presenilin
  • Tau
  • γ-Secretase


Dive into the research topics of 'Presenilin-1 regulates the expression of p62 to govern p62-dependent tau degradation'. Together they form a unique fingerprint.

Cite this