A presenilin 1 mutation associated with familial frontotemporal dementia inhibits γ-secretase cleavage of APP and notch

被引：83

作者：

Amtul, Z

Lewis, PA

Piper, S

Crook, R

Baker, M

Findlay, K

Singleton, A

Hogg, M

Younkin, L

Younkin, SG

Hardy, J

Hutton, M

Boeve, BF

Tang-Wai, D

Golde, TE

机构：

[1] Mayo Clin Jacksonville, Dept Neurosci & Pharmacol, Jacksonville, FL 32224 USA

[2] Mayo Clin & Mayo Fdn, Dept Neurol, Rochester, MN 55905 USA

[3] Mayo Clin & Mayo Fdn, Mayo Alzheimers Dis Res Ctr, Rochester, MN 55905 USA

来源：

NEUROBIOLOGY OF DISEASE | 2002年 / 9卷 / 02期

关键词：

D O I：

10.1006/nbdi.2001.0473

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

A novel presenilin 1 mutation, insR352, associated with a frontal temporal dementia phenotype has been identified (E. A. Rogaeva et al., 2001, Neurology 57, 621-625). This mutation does not increase Abeta42 levels, but instead acts as dominant negative presenilin, decreasing amyloid 13 protein (Abeta) production by inhibiting gamma-secretase cleavage of the Abeta precursor. The distinct clinical phenotype associated with this mutation suggests that chronic partial inhibition of gamma-secretase activity may result in neurodegeneration. (C) 2002 Elsevier Science (USA).

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页码：269 / 273

页数：5

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