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

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

Author information

1
Department of Agricultural Biotechnology, Seoul National University, Seoul 08826, Republic of Korea.
2
Department of Biological Sciences, Konkuk University, Seoul 05029, Republic of Korea.
3
Department of Neurobiology and Behavior, University of California-Irvine, Irvine, CA 92697, USA.
4
Research Institute for Veterinary Science, Seoul National University, Seoul 08826, Republic of Korea.

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

PMID:
29714053
DOI:
10.1002/mnfr.201800240

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