Siyoung Lee1, Bo-Ryoung Choi2, Jisung Kim1, Frank M. LaFerla3, Jung Han Yoon Park1, Jung-Soo Han2, Ki Won Lee1,* and Jiyoung Kim1,4,*
1Department of Agricultural Biotechnology, Seoul National University, Seoul 08826, Republic of Korea
2Department of Biological Sciences, Konkuk University, Seoul 05029, Republic of Korea
3Department of Neurobiology and Behavior, University of California-Irvine, Irvine, CA 92697, USA
4Research Institute for Veterinary Science, Seoul National University, Seoul 08826, Republic of Korea
S.L. and B-R.C. contributed equally to this work.
*To whom correspondence may be addressed.
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 a nd 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 treatmentupregulates CHIP and has the potential to decrease the accumulation of Aβand tau in patients with AD
Keywords: Alzheimer’s disease, amyloid-β, CHIP, sulforaphane, tau