title: Disease-modified glycogen synthase kinase-3β intervention by melatonin arrests the pathology and memory deficits in an Alzheimer's animal model.
abstract: The current therapies for Alzheimer's disease (AD) are merely palliative that cannot arrest the pathologic progression of the disease. Therefore, it is critical to develop treatments that can target the disease-modifying molecule(s). In the present study, we found that treatment of tg2576 mice with melatonin from 4-8 months of age did not improve the pathology or behavioral performance of the mice. However, remarkable attenuation of tau and β-amyloid pathologies with memory improvement were observed when melatonin was supplied from the age of 8-12 months or 4-12 months of the mice; more importantly, the improvements were still significant when the mice survived to old age. We also found that the disease stage-specific alteration of glycogen synthase kinase-3β (GSK-3β) but not protein phosphatase-2A, was correlated with the alterations of the pathology and behavior, and the timely targeting of GSK-3β was critical for the efficacy of melatonin. Our finding suggests that melatonin treatment only at proper timing could arrest AD by targeting the activated GSK-3β, which provides primary evidence for the importance and strategy in developing disease-modifying interventions of AD.
authors: Pathophysiology Department, Key Laboratory of Education Ministry for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.
authors: Cai-Xia
authors: CX
authors: Peng
authors: Juan
authors: J
authors: Hu
authors: Dan
authors: D
authors: Liu
authors: Xiao-Ping
authors: XP
authors: Hong
authors: Yuan-Yuan
authors: YY
authors: Wu
authors: Ling-Qiang
authors: LQ
authors: Zhu
authors: Jian-Zhi
authors: JZ
authors: Wang
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D000818:Animals; D004195:Disease Models, Animal; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D008297:Male; D008550:Melatonin / Q000494:pharmacology / Q000627:therapeutic use*; D008569:Memory Disorders / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D051379:Mice; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D047428:Protein Kinase Inhibitors; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3; D008550:Melatonin