Participation of Presenilin 2 in Apoptosis: Enhanced Basal Activity Conferred by an Alzheimer Mutation

Overexpression of the familial Alzheimer's disease gene Presenilin 2 (PS2) in nerve growth factor-differentiated PC12 cells increased apoptosis induced by trophic factor withdrawal or β-amyloid. Transfection of antisense PS2 conferred protection against apoptosis induced by trophic withdrawal i...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 1996-12, Vol.274 (5293), p.1710-1713
Main Authors: Wolozin, Benjamin, Iwasaki, Katsunori, Vito, Pasquale, Ganjei, J. Kelly, Lacanà, Emanuela, Sunderland, Trey, Zhao, Boyu, Kusiak, John W., Wasco, Wilma, D'Adamio, Luciano
Format: Article
Language:English
Subjects:
Alzheimer Disease - genetics
Alzheimer's disease
Alzheimers disease
Amyloid beta-Peptides - pharmacology
Amyloid beta-Protein Precursor - metabolism
Amyloid beta-Protein Precursor - pharmacology
Animals
Apoptosis
Biological and medical sciences
Cell death
Cell lines
Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
DNA, Antisense - genetics
Genetic aspects
Genetic mutation
Genetics
GTP-Binding Protein alpha Subunits, Gi-Go - physiology
GTP-Binding Protein alpha Subunits, Gs - physiology
Humans
Medical research
Medical sciences
Membrane Proteins - genetics
Membrane Proteins - physiology
Mutation
Nerve Growth Factors - pharmacology
Neurology
Neurons
Neurons - cytology
PC12 Cells
Peptide Fragments - pharmacology
Pertussis Toxin
Presenilin-2
Presenilins
Rats
T lymphocytes
Transfection
Virulence Factors, Bordetella - pharmacology
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Summary:Overexpression of the familial Alzheimer's disease gene Presenilin 2 (PS2) in nerve growth factor-differentiated PC12 cells increased apoptosis induced by trophic factor withdrawal or β-amyloid. Transfection of antisense PS2 conferred protection against apoptosis induced by trophic withdrawal in nerve growth factor-differentiated or amyloid precursor protein-expressing PC12 cells. The apoptotic cell death induced by PS2 protein was sensitive to pertussis toxin, suggesting that heterotrimeric GTP-binding proteins are involved. A PS2 mutation associated with familial Alzheimer's disease was found to generate a molecule with enhanced basal apoptotic activity. This gain of function might accelerate the process of neurodegeneration that occurs in Alzheimer's disease, leading to the earlier age of onset characteristic of familial Alzheimer's disease.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.274.5293.1710