title: Modulation of FGF receptor signaling as an intervention and potential therapy for myelin breakdown in Alzheimer's disease.
abstract: Alzheimer's disease (AD) is the most common neurodegenerative disease and oligodendrocyte degeneration and white matter damage play a critical role in the pathogenesis of AD. FGF/FGF receptor signaling have been implicated in diverse cellular processes including cell apoptosis, survival, adhesion, migration, differentiation, and proliferation, as well as key regulators of the development of the central nervous system (including in axon guidance and synaptogenesis) via multiple signal pathways. It has been demonstrated that FGF infusion or gene transfer restores neurogenesis in subventricular zone and hippocampal functions in aged mice and mouse models of AD and has therapeutic implications for neurocognitive disorders. Besides, FGF receptor signaling in oligodendrocytes regulates myelin sheath thickness via Erk1/2 MAPK and PI3K/Akt/mTOR signaling, which sequentially regulates progression through distinct stages of oligodendrocyte differentiation. The effect could be effectively antagonized by the potent, selective tyrosine kinase inhibitor of FGF receptor activity. We therefore propose that modulation of FGF receptor signaling will suppress the development of oligodendrocyte degeneration and myelin breakdown or white matter damage in mouse models or patients of AD and improve or restore the pathological and clinical symptoms of cognitive decline, and FGF receptor signaling with its inhibitors and/or gene transfer would serve as an intervention and potential therapy for myelin breakdown and cognitive decline in AD.
authors: Department of Physiology, Third Military Medical University, Chongqing 400038, China.
authors: Jia-Su
authors: JS
authors: Li
authors: Zhong-Xiang
authors: ZX
authors: Yao
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009186:Myelin Sheath / Q000187:drug effects* / Q000473:pathology*; D017468:Receptors, Fibroblast Growth Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D017468:Receptors, Fibroblast Growth Factor