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The role of Fyn in the pathogenic pr...

Minami, Stephanie Sakura.

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The role of Fyn in the pathogenic processes of Alzheimer's disease.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	The role of Fyn in the pathogenic processes of Alzheimer's disease./
作者:	Minami, Stephanie Sakura.
面頁冊數:	128 p.
附註:	Source: Dissertation Abstracts International, Volume: 71-04, Section: B, page: 2201.
Contained By:	Dissertation Abstracts International71-04B.
標題:	Biology, Neurobiology. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3397591
ISBN:	9781109696172

The role of Fyn in the pathogenic processes of Alzheimer's disease.
Minami, Stephanie Sakura.

The role of Fyn in the pathogenic processes of Alzheimer's disease. - 128 p.

Source: Dissertation Abstracts International, Volume: 71-04, Section: B, page: 2201.

Thesis (Ph.D.)--Georgetown University, 2010.

The two main pathological hallmarks of Alzheimer's disease are amyloid plaques and neurofibrillary tangles. There is evidence supporting the hypothesis that the accumulation of Abeta, which makes up the core of amyloid plaques, triggers subsequent hyperphosphorylation of tau, leading to the formation of neurofibrillary tangles. However, the molecular mechanisms underlying the connection between Abeta and tau pathologies remain unclear. Fyn is a tyrosine kinase upregulated in Alzheimer's disease which co-localizes with phosphorylated tau and neurofibrillary tangles. Recent studies have also implicated a role for Fyn in Abeta-mediated neurotoxicity. However, whether Fyn directly leads to the phosphorylation of tau, or to alteration in amyloid precursor protein (APP) processing to generate Abeta, is unknown.

ISBN: 9781109696172Subjects--Topical Terms:

1681328
Biology, Neurobiology.

The role of Fyn in the pathogenic processes of Alzheimer's disease.
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245 1 4 $a The role of Fyn in the pathogenic processes of Alzheimer's disease.
300 $a 128 p.
500 $a Source: Dissertation Abstracts International, Volume: 71-04, Section: B, page: 2201.
500 $a Adviser: G. William Rebeck.
502 $a Thesis (Ph.D.)--Georgetown University, 2010.
520 $a The two main pathological hallmarks of Alzheimer's disease are amyloid plaques and neurofibrillary tangles. There is evidence supporting the hypothesis that the accumulation of Abeta, which makes up the core of amyloid plaques, triggers subsequent hyperphosphorylation of tau, leading to the formation of neurofibrillary tangles. However, the molecular mechanisms underlying the connection between Abeta and tau pathologies remain unclear. Fyn is a tyrosine kinase upregulated in Alzheimer's disease which co-localizes with phosphorylated tau and neurofibrillary tangles. Recent studies have also implicated a role for Fyn in Abeta-mediated neurotoxicity. However, whether Fyn directly leads to the phosphorylation of tau, or to alteration in amyloid precursor protein (APP) processing to generate Abeta, is unknown.
520 $a We first investigated the effect of Fyn on APP processing and whether this effect is mediated through Dab1, an adaptor protein which is phosphorylated by Fyn and decreases Abeta production. Using in vitro culture models (COS7) and Fyn knock-out mice, we found that Fyn increases cell surface APP and promotes alpha-secretase processing of APP, in part through Dab1. We next determined the subcellular localization of the APP-Dab1-Fyn interactions using lipid raft isolation from brains and primary neurons, and found that Fyn mediates the interaction between APP and Dab1 by regulating their phosphorylation and localization in lipid rafts. Finally, we aimed to determine the effect of Fyn inhibition on pathological and behavioral symptoms in a triple transgenic (3xTg) model of Alzheimer's disease if Fyn exerts opposing effects on Abeta production and tau phosphorylation. We found that genetic and pharmacological inhibition of Fyn in 3xTg mice resulted in a decrease in tau phosphorylation and an increase in Abeta production accompanied by a deficit in spatial learning. These effects were age and/or pathology dependent, underscoring the importance of considering age and/or disease burden when determining appropriate treatment. In conclusion, we establish a complex role for Fyn in mediating both APP processing and tau phosphorylation in a physiological environment as well as under the pathological conditions of Alzheimer's disease.
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773 0 $t Dissertation Abstracts International $g 71-04B.
790 1 0 $a Rebeck, G. William, $e advisor
790 1 0 $a Turner, R. Scott $e committee member
790 1 0 $a Lim, Seung $e committee member
790 1 0 $a Pak, Daniel T.S. $e committee member
790 1 0 $a Wrathall, Jean R. $e committee member
790 1 0 $a Manaye, Kebreten F. $e committee member
790 $a 0076
791 $a Ph.D.
792 $a 2010
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3397591