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-beta (A beta) and tau, the two main pathological factors in Alzheimer's disease (AD). Methods and results: A triple transgenic mouse model of AD (3 x Tg-AD) is used to study the effect of sulforaphane. Oral gavage of sulforaphane reduces protein levels of monomeric and polymeric forms of A beta as well as tau and phosphorylated tau in 3 x Tg-AD mice. However, sulforaphane treatment do not affect mRNA expression of amyloid precursor protein or tau. As previous studies show that A beta 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 x Tg-AD mice suggest that sulforaphane treatment increase CHIP level and clear the accumulation of A beta and tau. Finally, sulforaphane ameliorated memory deficits in 3 x 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 A beta and tau in patients with AD.