TY - JOUR
T1 - Therapeutic potential and anti-amyloidosis mechanisms of tert-butylhydroquinone for Alzheimer's disease
AU - Akhter, Hasina
AU - Katre, Ashwini
AU - Li, Ling
AU - Liu, Xuebo
AU - Liu, Rui Ming
PY - 2011
Y1 - 2011
N2 - Alzheimer's disease (AD) is a major cause of dementia in the elderly with no effective treatment. Accumulation of amyloid-β peptide (Aβ) in the brain, one of the pathological features of AD, is considered to be a central disease-causing and disease-promoting event in AD. In this study, we showed that feeding male AβPP/PS1 transgenic mice, a well established mouse model of AD, with a diet containing phenolic antioxidant tert-butylhydroquinone (TBHQ) dramatically reduced brain Aβ load with no significant effect on the amounts of alpha- and beta-C-terminal fragments or full-length AβPP. Further studies showed that TBHQ diet inhibited the expression of plasminogen activator inhibitor-1 (PAI-1), a protease inhibitor which plays a critical role in brain Aβ accumulation in AD, accompanied by increases in the activities of tissue type and urokinase type plasminogen activators (tPA and uPA) as well as plasmin. Moreover, we showed that TBHQ diet increased the expression of low density lipoprotein related protein-1, a multi ligand endocytotic receptor involved in transporting Aβ out of the brain, and plasma Aβ40 and Aβ42 levels. We also showed that TBHQ diet increased the concentration of glutathione, an important antioxidant, and suppressed the expression of NADPH oxidase 2 as well as lipid peroxidation. Collectively, our data suggest that TBHQ may have therapeutic potential for AD by increasing brain antioxidant capacity/reducing oxidative stress level and by stimulating Aβ degradation/clearance pathways.
AB - Alzheimer's disease (AD) is a major cause of dementia in the elderly with no effective treatment. Accumulation of amyloid-β peptide (Aβ) in the brain, one of the pathological features of AD, is considered to be a central disease-causing and disease-promoting event in AD. In this study, we showed that feeding male AβPP/PS1 transgenic mice, a well established mouse model of AD, with a diet containing phenolic antioxidant tert-butylhydroquinone (TBHQ) dramatically reduced brain Aβ load with no significant effect on the amounts of alpha- and beta-C-terminal fragments or full-length AβPP. Further studies showed that TBHQ diet inhibited the expression of plasminogen activator inhibitor-1 (PAI-1), a protease inhibitor which plays a critical role in brain Aβ accumulation in AD, accompanied by increases in the activities of tissue type and urokinase type plasminogen activators (tPA and uPA) as well as plasmin. Moreover, we showed that TBHQ diet increased the expression of low density lipoprotein related protein-1, a multi ligand endocytotic receptor involved in transporting Aβ out of the brain, and plasma Aβ40 and Aβ42 levels. We also showed that TBHQ diet increased the concentration of glutathione, an important antioxidant, and suppressed the expression of NADPH oxidase 2 as well as lipid peroxidation. Collectively, our data suggest that TBHQ may have therapeutic potential for AD by increasing brain antioxidant capacity/reducing oxidative stress level and by stimulating Aβ degradation/clearance pathways.
KW - Alzheimer's disease
KW - amyloid-β degradation
KW - amyloid-β efflux
KW - antioxidant
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U2 - 10.3233/JAD-2011-110512
DO - 10.3233/JAD-2011-110512
M3 - Article
C2 - 21860091
AN - SCOPUS:80055056469
SN - 1387-2877
VL - 26
SP - 767
EP - 778
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
IS - 4
ER -