Participation of Presenilin 2 in apoptosis

Enhanced basal activity conferred by an Alzheimer mutation

Benjamin Wolozin, Katsunori Iwasaki, Pasquale Vito, J. Kelly Ganjei, Emanuela Lacanà, Trey Sunderland, Boyu Zhao, John W. Kusiak, Wilma Wasco, Luciano D'Adamio

Research output: Contribution to journalArticle

382 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1710-1712
Number of pages3
JournalScience
Volume274
Issue number5293
DOIs
StatePublished - Dec 6 1996
Externally publishedYes

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Presenilin-2
Alzheimer Disease
Apoptosis
Mutation
PC12 Cells
Nerve Growth Factor
Heterotrimeric GTP-Binding Proteins
Amyloid beta-Protein Precursor
Pertussis Toxin
Age of Onset
Amyloid
Transfection
Cell Death
Genes
Proteins

ASJC Scopus subject areas

  • General

Cite this

Wolozin, B., Iwasaki, K., Vito, P., Ganjei, J. K., Lacanà, E., Sunderland, T., ... D'Adamio, L. (1996). Participation of Presenilin 2 in apoptosis: Enhanced basal activity conferred by an Alzheimer mutation. Science, 274(5293), 1710-1712. https://doi.org/10.1126/science.274.5293.1710

Participation of Presenilin 2 in apoptosis : Enhanced basal activity conferred by an Alzheimer mutation. / Wolozin, Benjamin; Iwasaki, Katsunori; Vito, Pasquale; Ganjei, J. Kelly; Lacanà, Emanuela; Sunderland, Trey; Zhao, Boyu; Kusiak, John W.; Wasco, Wilma; D'Adamio, Luciano.

In: Science, Vol. 274, No. 5293, 06.12.1996, p. 1710-1712.

Research output: Contribution to journalArticle

Wolozin, B, Iwasaki, K, Vito, P, Ganjei, JK, Lacanà, E, Sunderland, T, Zhao, B, Kusiak, JW, Wasco, W & D'Adamio, L 1996, 'Participation of Presenilin 2 in apoptosis: Enhanced basal activity conferred by an Alzheimer mutation', Science, vol. 274, no. 5293, pp. 1710-1712. https://doi.org/10.1126/science.274.5293.1710
Wolozin B, Iwasaki K, Vito P, Ganjei JK, Lacanà E, Sunderland T et al. Participation of Presenilin 2 in apoptosis: Enhanced basal activity conferred by an Alzheimer mutation. Science. 1996 Dec 6;274(5293):1710-1712. https://doi.org/10.1126/science.274.5293.1710
Wolozin, Benjamin ; Iwasaki, Katsunori ; Vito, Pasquale ; Ganjei, J. Kelly ; Lacanà, Emanuela ; Sunderland, Trey ; Zhao, Boyu ; Kusiak, John W. ; Wasco, Wilma ; D'Adamio, Luciano. / Participation of Presenilin 2 in apoptosis : Enhanced basal activity conferred by an Alzheimer mutation. In: Science. 1996 ; Vol. 274, No. 5293. pp. 1710-1712.
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