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

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. Our previous findings identified sulforaphane as a critical modulator not only for acetylcholine but also BDNF production in a mouse model of Alzheimer's disease (AD). In this study, oral gavage of sulforaphane in a triple transgenic mouse model of AD (3 × Tg‐AD) reduces protein levels of amyloid‐β (Aβ) as well as tau and phosphorylated tau through the post‐translational modifications by upregulating the heat shock protein co‐chaperone CHIP. Sulforaphane may represent a promising and feasible preventive strategy in the treatment of AD.