Sulforaphane Upregulates the Heat Shock Protein Co-Chaperone CHIP and Clears Amyloid-β and Tau in a Mouse Model of Alzheimer's Disease

Mol Nutr Food Res. 2018 Jun;62(12):e1800240. doi: 10.1002/mnfr.201800240. Epub 2018 May 28.

Abstract

Scope: Sulforaphane is an herbal isothiocyanate enriched in cruciferous vegetables. Here, the authors investigate whether sulforaphane modulates the production of amyloid-β (Aβ) and tau, the two main pathological factors in Alzheimer's disease (AD).

Methods and results: A triple transgenic mouse model of AD (3 × Tg-AD) is used to study the effect of sulforaphane. Oral gavage of sulforaphane reduces protein levels of monomeric and polymeric forms of Aβ as well as tau and phosphorylated tau in 3 × Tg-AD mice. However, sulforaphane treatment do not affect mRNA expression of amyloid precursor protein or tau. As previous studies show that Aβ and tau metabolism are influenced by a heat shock protein (HSP) co-chaperone, C-terminus of HSP70-interacting protein (CHIP), the authors examine whether sulforaphane can modulate CHIP. The authors find that sulforaphane treatment increase levels of CHIP and HSP70. Furthermore, observations of CHIP-deficient primary neurons derived from 3 × Tg-AD mice suggest that sulforaphane treatment increase CHIP level and clear the accumulation of Aβ and tau. Finally, sulforaphane ameliorated memory deficits in 3 × Tg-AD mice as reveal by novel object/location recognition tests and contextual fear conditioning tests.

Conclusion: These results demonstrate that sulforaphane treatment upregulates CHIP and has the potential to decrease the accumulation of Aβ and tau in patients with AD.

Keywords: Alzheimer's disease; CHIP; amyloid-β; sulforaphane; tau.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / metabolism*
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Disease Models, Animal
  • Female
  • HSP70 Heat-Shock Proteins / metabolism
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Isothiocyanates / pharmacology*
  • Memory Disorders / drug therapy
  • Mice, Transgenic
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurons / pathology
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism*
  • Up-Regulation
  • tau Proteins / metabolism*

Substances

  • Amyloid beta-Peptides
  • HSP70 Heat-Shock Proteins
  • Isothiocyanates
  • Mapt protein, mouse
  • tau Proteins
  • Stub1 protein, mouse
  • Ubiquitin-Protein Ligases
  • sulforafan