TY - JOUR
T1 - Oral supplementation with Leu-Ile, a hydrophobic dipeptide, prevents the impairment of memory induced by amyloid beta in mice via restraining the hyperphosphorylation of extracellular signal-regulated kinase
AU - Alkam, Tursun
AU - Nitta, Atsumi
AU - Furukawa-Hibi, Yoko
AU - Niwa, Minae
AU - Mizoguchi, Hiroyuku
AU - Yamada, Kiyofumi
AU - Nabeshima, Toshitaka
N1 - Funding Information:
This work was supported, in part, by the Japan-China Sasakawa Medical fellowship (to Tursun Alkam); by the Uehara Memorial Foundation fellowship for Foreign Researchers in Japan (to Tursun Alkam); by a Grant-in-Aid for the 21st Century Center of Excellence Program “Integrated Molecular Medicine for Neuronal and Neoplastic Disorders” and “Academic Frontier Project for Private Universities (2007–2011)” from the Ministry of Education, Culture, Sports, Science and Technology of Japan; by Comprehensive Research on Aging and Health from the Ministry of Health, Labor and Welfare of Japan; by the Japan-Canada Joint Health Research Program and Japan-France Joint Health Research Program (Joint Project from Japan Society for the Promotion of Science); and by an International Research Project Supported by the Meijo Asian Research Center.
PY - 2010/7
Y1 - 2010/7
N2 - Restraining the toxic pathways of amyloid beta peptide (Aβ) by daily supplementation with dietary products has been shown effective in preventing cognitive decline. In this study, we examined the effects of the orally administered Leu-Ile, a hydrophobic dipeptide, on the neurotoxicity of Aβ25-35 in mice. Chronic daily treatment with Leu-Ile prevented the Aβ25-35-induced protein nitration and impairment of novel object recognition memory in mice. Protein nitration in the hippocampus induced by Aβ25-35 was associated with the hyperphosphorylation of extracellular signal-regulated kinase (ERK) which was found responsible for the over-expression of inducible nitric oxide synthase. Sub-chronic treatment with Leu-Ile prevented the Aβ25-35-induced hyperphosphorylation of ERK and protein nitration in the hippocampus. The results suggested that with the protective property against the neurotoxicity of Aβ25-35, Leu-Ile could be considered as a candidate for the dietary supplementation in the prevention of Aβ-related impairment of recognition memory.
AB - Restraining the toxic pathways of amyloid beta peptide (Aβ) by daily supplementation with dietary products has been shown effective in preventing cognitive decline. In this study, we examined the effects of the orally administered Leu-Ile, a hydrophobic dipeptide, on the neurotoxicity of Aβ25-35 in mice. Chronic daily treatment with Leu-Ile prevented the Aβ25-35-induced protein nitration and impairment of novel object recognition memory in mice. Protein nitration in the hippocampus induced by Aβ25-35 was associated with the hyperphosphorylation of extracellular signal-regulated kinase (ERK) which was found responsible for the over-expression of inducible nitric oxide synthase. Sub-chronic treatment with Leu-Ile prevented the Aβ25-35-induced hyperphosphorylation of ERK and protein nitration in the hippocampus. The results suggested that with the protective property against the neurotoxicity of Aβ25-35, Leu-Ile could be considered as a candidate for the dietary supplementation in the prevention of Aβ-related impairment of recognition memory.
KW - Amyloid beta (25-35)
KW - Extracellular signal-regulated kinase
KW - Inducible nitric oxide synthase
KW - Novel object recognition memory
KW - Protein nitration
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U2 - 10.1016/j.bbr.2010.02.028
DO - 10.1016/j.bbr.2010.02.028
M3 - Article
C2 - 20171988
AN - SCOPUS:77952322580
SN - 0166-4328
VL - 210
SP - 184
EP - 190
JO - Behavioural Brain Research
JF - Behavioural Brain Research
IS - 2
ER -