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.
journal_name
Med Hypothesesjournal_title
Medical hypothesesauthors
Li JS,Yao ZXdoi
10.1016/j.mehy.2012.12.008subject
Has Abstractpub_date
2013-04-01 00:00:00pages
341-4issue
4eissn
0306-9877issn
1532-2777pii
S0306-9877(12)00557-9journal_volume
80pub_type
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journal_title：Medical hypotheses
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pub_type： 杂志文章
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更新日期：2007-01-01 00:00:00
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更新日期：2012-08-20 00:00:00
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pub_type： 杂志文章
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更新日期：2006-01-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
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更新日期：2004-01-01 00:00:00
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pub_type： 杂志文章
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更新日期：2009-11-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2009.10.013
更新日期：2010-03-01 00:00:00
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pub_type： 杂志文章
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journal_title：Medical hypotheses
pub_type： 杂志文章
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pub_type： 杂志文章
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更新日期：2020-10-01 00:00:00
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pub_type： 杂志文章
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journal_title：Medical hypotheses
pub_type： 历史文章,杂志文章
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更新日期：2006-01-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
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更新日期：2015-11-01 00:00:00
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journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2012.05.031
更新日期：2012-09-01 00:00:00
