Estrogens stabilize mitochondrial function and protect neural cells against the pro-apoptotic action of mutant presenilin-1

Mark P. Mattson, Nic Robinson, Qing Guo

Research output: Contribution to journalArticle

Abstract

MUTATIONS in presenilin-1 (PS-1) account for approximately half the cases of autosomal dominant early-onset Alzheimer's disease (AD). Recent data indicate that PS-1 mutations may render neurons vulnerable to apoptosis induced by various insults. We now report that 17β-estradiol, which appears to reduce the risk of sporadic AD, protects cultured PC12 cells expressing mutant PS-1 against apoptosis induced by trophic factor withdrawal (TFW) and exposure to amyloid β-peptide 25-35 (Aβ). Estriol also provided significant protection against apoptosis induced by TFW and Aβ, whereas corticosterone was ineffective. 17β-Estradiol prevented decreases in mitochondrial transmembrane potential and energy charge/redox state following exposure of cells to TFW and Aβ in control cell lines and lines expressing mutant PS-1, suggesting an action in the apoptotic pathway upstream of mitochondrial alterations. Aβ caused an increase in mitochondrial reactive oxygen species which was enhanced by mutant PS-1, and suppressed by 17β-estradiol. The ability of 17β-estradiol to preserve mitochondrial function, suppress oxidative stress, and counteract the pro-apoptotic actions of mutant PS-1 suggests a generalized neuroprotective action of estrogens in both sporadic and inherited forms of AD.

Original languageEnglish (US)
Pages (from-to)3817-3821
Number of pages5
JournalNeuroReport
Volume8
Issue number17
StatePublished - 1997
Externally publishedYes

Fingerprint

Presenilin-1
Estrogens
Estradiol
Alzheimer Disease
Apoptosis
Estriol
Aptitude
PC12 Cells
Corticosterone
Amyloid
Membrane Potentials
Oxidation-Reduction
Cultured Cells
Reactive Oxygen Species
Oxidative Stress
Neurons
Cell Line
Peptides
Mutation

Keywords

  • 17β- Estradiol
  • Alzheimer's disease
  • Amyloid β-peptide
  • Corticosterone
  • Lipid peroxidation
  • Mitochondrial transmembrane potential
  • Peroxynitrite

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Estrogens stabilize mitochondrial function and protect neural cells against the pro-apoptotic action of mutant presenilin-1. / Mattson, Mark P.; Robinson, Nic; Guo, Qing.

In: NeuroReport, Vol. 8, No. 17, 1997, p. 3817-3821.

Research output: Contribution to journalArticle

Mattson, Mark P. ; Robinson, Nic ; Guo, Qing. / Estrogens stabilize mitochondrial function and protect neural cells against the pro-apoptotic action of mutant presenilin-1. In: NeuroReport. 1997 ; Vol. 8, No. 17. pp. 3817-3821.
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