Subcutaneous liraglutide ameliorates methylglyoxal-induced Alzheimer-like tau pathology and cognitive impairment by modulating tau hyperphosphorylation and glycogen synthase kinase-3β.
Memory deterioration and synapse damage with accumulation of β-amyloid and hyperphosphorylated tau are hallmark lesions of Alzheimer's disease (AD). Methylglyoxal (MG), a key intermediate of glucose metabolism, is elevated in AD brains and modifies Aβ42, increasing misfolding and leading to the accumulation of senile plaques. Liraglutide, an analog of glucagon-like peptide-1 (GLP-1), is neurotrophic and neuroprotective. However, whether liraglutide can protect against AD-like memory-related deficits and tau hyperphosphorylation caused by MG in vivo is not known. Here, we report that MG induces tau hyperphosphorylation and causes ultrastructural hippocampal damage and cognitive impairment in C57BL/6J mice. Liraglutide reduced these effects via activation of the protein kinase B and glycogen synthase kinase-3β pathways. Our data reveal that liraglutide may alleviate AD-like cognitive impairment by decreasing the phosphorylation of tau.
Department of Endocrinology, Fujian Institute of Endocrinology, Fujian Medical University Union Hospital Fuzhou, Fujian, People's Republic of China.
Liqin
L
Qi
Department of Pharmacology, College of Pharmacy, Fujian Medical University Fuzhou, Fujian, People's Republic of China.
Zhou
Z
Chen
Department of Endocrinology, Fujian Institute of Endocrinology, Fujian Medical University Union HospitalFuzhou, Fujian, People's Republic of China; Department of Geriatrics, Fujian Medical University Union HospitalFuzhou, Fujian, People's Republic of China.
Yanping
Y
Wang
Department of Geriatrics, Fujian Medical University Union Hospital Fuzhou, Fujian, People's Republic of China.
Xiaoying
X
Liu
Department of Endocrinology, Fujian Institute of Endocrinology, Fujian Medical University Union Hospital Fuzhou, Fujian, People's Republic of China.
Xiaohong
X
Liu
Department of Endocrinology, Fujian Institute of Endocrinology, Fujian Medical University Union Hospital Fuzhou, Fujian, People's Republic of China.
Linfang
L
Ke
Department of Pharmacology, College of Pharmacy, Fujian Medical University Fuzhou, Fujian, People's Republic of China.
Zhongjie
Z
Zheng
Department of Endocrinology, Fujian Institute of Endocrinology, Fujian Medical University Union Hospital Fuzhou, Fujian, People's Republic of China.
Xiaowei
X
Lin
Department of Endocrinology, Fujian Institute of Endocrinology, Fujian Medical University Union Hospital Fuzhou, Fujian, People's Republic of China.
Yu
Y
Zhou
Department of Endocrinology, Fujian Institute of Endocrinology, Fujian Medical University Union Hospital Fuzhou, Fujian, People's Republic of China.
Lijuan
L
Wu
Department of Endocrinology, Fujian Institute of Endocrinology, Fujian Medical University Union HospitalFuzhou, Fujian, People's Republic of China; The Institute of Aging Health Science, Fujian Medical UniversityFuzhou, Fujian, People's Republic of China.
Libin
L
Liu
Alzheimer’s disease; glucagon-like peptide-1; glycogen synthase kinase-3β; methylglyoxal; tau protein