BACE (β-secretase) modulates the processing of APLP2 in vivo

L. Pastorino; A. F. Ikin; S. Lamprianou; N. Vacaresse; J. P. Revelli; K. Platt; P. Paganetti; P. M. Mathews; S. Harroch; J. D. Buxbaum

doi:10.1016/j.mcn.2003.12.013

BACE (β-secretase) modulates the processing of APLP2 in vivo

L. Pastorino
, A. F. Ikin
, S. Lamprianou
, N. Vacaresse
, J. P. Revelli
, K. Platt
, P. Paganetti
, P. M. Mathews
, S. Harroch
, J. D. Buxbaum

Research output: Contribution to journal › Article › peer-review

105 Scopus citations

Abstract

BACE is an aspartyl protease that cleaves the amyloid precursor protein (APP) at the β-secretase cleavage site and is involved in Alzheimer's disease. The aim of our study was to determine whether BACE affects the processing of the APP homolog APLP2. To this end, we developed BACE knockout mice with a targeted insertion of the gene for β-galactosidase. BACE appeared to be exclusively expressed in neurons as determined by differential staining. BACE was expressed in specific areas in the cortex, hippocampus, cerebellum, pons, and spinal cord. APP processing was altered in the BACE knockouts with Aβ levels decreasing. The levels of APLP2 proteolytic products were decreased in BACE KO mice, but increased in BACE transgenic mice. Overexpression of BACE in cultured cells led to increased APLP2 processing. Our results strongly suggest that BACE is a neuronal protein that modulates the processing of both APP and APLP2.

Original language	English
Pages (from-to)	642-649
Number of pages	8
Journal	Molecular and Cellular Neuroscience
Volume	25
Issue number	4
DOIs	https://doi.org/10.1016/j.mcn.2003.12.013
State	Published - Apr 2004

Keywords

AD
AICD
APLP
APP
Alzheimer's disease
Amyloid precursor like protein
Amyloid precursor protein
Aβ
BACE
HET
Heterozygous
KO
Knockout
Soluble APLP2
TG
Transgenic
WT
Wild-type
sAPLP2
β-amyloid peptide
β-site APP cleaving enzyme

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10.1016/j.mcn.2003.12.013

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@article{2e0b38f046e046ef98349e9d945a86b9,

title = "BACE (β-secretase) modulates the processing of APLP2 in vivo",

abstract = "BACE is an aspartyl protease that cleaves the amyloid precursor protein (APP) at the β-secretase cleavage site and is involved in Alzheimer's disease. The aim of our study was to determine whether BACE affects the processing of the APP homolog APLP2. To this end, we developed BACE knockout mice with a targeted insertion of the gene for β-galactosidase. BACE appeared to be exclusively expressed in neurons as determined by differential staining. BACE was expressed in specific areas in the cortex, hippocampus, cerebellum, pons, and spinal cord. APP processing was altered in the BACE knockouts with Aβ levels decreasing. The levels of APLP2 proteolytic products were decreased in BACE KO mice, but increased in BACE transgenic mice. Overexpression of BACE in cultured cells led to increased APLP2 processing. Our results strongly suggest that BACE is a neuronal protein that modulates the processing of both APP and APLP2.",

keywords = "AD, AICD, APLP, APP, Alzheimer's disease, Amyloid precursor like protein, Amyloid precursor protein, Aβ, BACE, HET, Heterozygous, KO, Knockout, Soluble APLP2, TG, Transgenic, WT, Wild-type, sAPLP2, β-amyloid peptide, β-site APP cleaving enzyme",

author = "L. Pastorino and Ikin, \{A. F.\} and S. Lamprianou and N. Vacaresse and Revelli, \{J. P.\} and K. Platt and P. Paganetti and Mathews, \{P. M.\} and S. Harroch and Buxbaum, \{J. D.\}",

note = "Funding Information: Authors are grateful to Stephen Schmidt, for helping with ELISA. This work was supported by The National Institutes of Aging grants AG10491 (to JDB), AG14996 (to JDB) and AG002219 (to JDB). ",

year = "2004",

month = apr,

doi = "10.1016/j.mcn.2003.12.013",

language = "English",

volume = "25",

pages = "642--649",

journal = "Molecular and Cellular Neuroscience",

issn = "1044-7431",

publisher = "Academic Press Inc.",

number = "4",

}

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T1 - BACE (β-secretase) modulates the processing of APLP2 in vivo

AU - Pastorino, L.

AU - Ikin, A. F.

AU - Lamprianou, S.

AU - Vacaresse, N.

AU - Revelli, J. P.

AU - Platt, K.

AU - Paganetti, P.

AU - Mathews, P. M.

AU - Harroch, S.

AU - Buxbaum, J. D.

N1 - Funding Information: Authors are grateful to Stephen Schmidt, for helping with ELISA. This work was supported by The National Institutes of Aging grants AG10491 (to JDB), AG14996 (to JDB) and AG002219 (to JDB).

PY - 2004/4

Y1 - 2004/4

N2 - BACE is an aspartyl protease that cleaves the amyloid precursor protein (APP) at the β-secretase cleavage site and is involved in Alzheimer's disease. The aim of our study was to determine whether BACE affects the processing of the APP homolog APLP2. To this end, we developed BACE knockout mice with a targeted insertion of the gene for β-galactosidase. BACE appeared to be exclusively expressed in neurons as determined by differential staining. BACE was expressed in specific areas in the cortex, hippocampus, cerebellum, pons, and spinal cord. APP processing was altered in the BACE knockouts with Aβ levels decreasing. The levels of APLP2 proteolytic products were decreased in BACE KO mice, but increased in BACE transgenic mice. Overexpression of BACE in cultured cells led to increased APLP2 processing. Our results strongly suggest that BACE is a neuronal protein that modulates the processing of both APP and APLP2.

AB - BACE is an aspartyl protease that cleaves the amyloid precursor protein (APP) at the β-secretase cleavage site and is involved in Alzheimer's disease. The aim of our study was to determine whether BACE affects the processing of the APP homolog APLP2. To this end, we developed BACE knockout mice with a targeted insertion of the gene for β-galactosidase. BACE appeared to be exclusively expressed in neurons as determined by differential staining. BACE was expressed in specific areas in the cortex, hippocampus, cerebellum, pons, and spinal cord. APP processing was altered in the BACE knockouts with Aβ levels decreasing. The levels of APLP2 proteolytic products were decreased in BACE KO mice, but increased in BACE transgenic mice. Overexpression of BACE in cultured cells led to increased APLP2 processing. Our results strongly suggest that BACE is a neuronal protein that modulates the processing of both APP and APLP2.

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KW - AICD

KW - APLP

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KW - Amyloid precursor like protein

KW - Amyloid precursor protein

KW - Aβ

KW - BACE

KW - HET

KW - Heterozygous

KW - KO

KW - Knockout

KW - Soluble APLP2

KW - TG

KW - Transgenic

KW - WT

KW - Wild-type

KW - sAPLP2

KW - β-amyloid peptide

KW - β-site APP cleaving enzyme

UR - https://www.scopus.com/pages/publications/11144355408

U2 - 10.1016/j.mcn.2003.12.013

DO - 10.1016/j.mcn.2003.12.013

M3 - Article

C2 - 15080893

AN - SCOPUS:11144355408

SN - 1044-7431

VL - 25

SP - 642

EP - 649

JO - Molecular and Cellular Neuroscience

JF - Molecular and Cellular Neuroscience

IS - 4

ER -

BACE (β-secretase) modulates the processing of APLP2 in vivo

Abstract

Keywords

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