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

Neuroreport
M P MattsonQ Guo

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 17beta-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 beta-peptide 25-35 (Abeta). Estriol also provided significant protection against apoptosis induced by TFW and Abeta, whereas corticosterone was ineffective. 17beta-Estradiol prevented decreases in mitochondrial transmembrane potential and energy charge/redox state following exposure of cells to TFW and Abeta in control cell lines and lines expressing mutant PS-1, suggesting an action in the apoptotic pathway upstream of mitochondrial alterations. Abeta caused an increase in mitochondrial reactive oxygen species which was enhanced by mutant PS-1, and suppressed by 17beta-estradiol. The ability of 17beta-estradiol to preserve mitochondrial function, suppress oxidative stress, and counteract the pro-apoptotic actions of mutant PS-1 suggests a generalized neuroprotective ...Continue Reading

References

Dec 1, 1994·Hormones and Behavior·R C MirandaD Toran-Allerand
Oct 1, 1996·Brain Pathology·C W Cotman, J H Su
Jan 1, 1997·Immunology Today·G KroemerS A Susin
Apr 1, 1997·Trends in Neurosciences·J Hardy

❮ Previous
Next ❯

Citations

Jan 26, 2005·Cell and Tissue Research·Horst ClaassenBodo Kurz
Jan 1, 2013·Journal of Bioenergetics and Biomembranes·António J M MorenoMaria S Santos
Mar 1, 2012·Journal of Physiology and Biochemistry·Suncica PetrovskaVladimir Jurisic
Dec 23, 2003·Neurochemistry International·Fang BaChristina G Benishin
Feb 15, 2001·European Journal of Pharmacology·D MaimoneL M Grimaldi
Oct 21, 2000·Progress in Neurobiology·L M Garcia-SeguraL L DonCarlos
Aug 26, 2000·Experimental Gerontology·S Gandy, K Duff
Jan 25, 2003·Experimental Gerontology·J A DykensK Gordon
May 19, 2000·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·P S Green, J W Simpkins
Apr 13, 1999·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·M P Mattson, W A Pedersen
Mar 15, 2000·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·A BrusadelliA Maggi
Nov 25, 2003·The Journal of Steroid Biochemistry and Molecular Biology·Allen KaasikAlexander Zharkovsky
Sep 4, 2004·Antioxidants & Redox Signaling·Atsushi TakedaMark A Smith
Aug 7, 1998·Neuroreport·M C MoniciG Vita
Nov 24, 1999·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·C CulmseeJ Krieglstein
Jun 18, 2002·Journal of Cellular and Molecular Medicine·B. O. Popescu, Maria Ankarcrona
Dec 30, 2010·American Journal of Physiology. Endocrinology and Metabolism·Daniel A KaneRonald N Cortright
May 17, 2012·Dementia and Geriatric Cognitive Disorders Extra·Astrid M HooghiemstraErik J A Scherder
Jul 29, 2000·Biochemical and Biophysical Research Communications·T NiikuraI Nishimoto
Jul 26, 2013·Journal of Neurotrauma·Yvette P ConleyDianxu Ren
Apr 1, 2014·The Journal of Endocrinology·Gabriela Capllonch-AmerFrancisco J García-Palmer
Mar 17, 2004·Proceedings of the National Academy of Sciences of the United States of America·Shao-Hua YangJames W Simpkins
Feb 27, 2003·Proceedings of the National Academy of Sciences of the United States of America·Jon Nilsen, Roberta Diaz Brinton
Jul 26, 2011·Neurobiology of Disease·Eun Ji GongJaewon Lee
Nov 26, 2009·Biochimica Et Biophysica Acta·James W SimpkinsJames A Dykens
Apr 25, 2000·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·P D Hurn, I M Macrae
Feb 16, 2008·Frontiers in Neuroendocrinology·Jon Nilsen
May 22, 2007·Brain Research Reviews·James W Simpkins, James A Dykens
Apr 5, 2012·Current Gerontology and Geriatrics Research·Joseph H LeeNicole Schupf
Jul 11, 2006·Experimental Cell Research·Vassilia-Ismini AlexakiElias Castanas
Jan 18, 2006·The Journal of Steroid Biochemistry and Molecular Biology·Vasilia-Ismini AlexakiElias Castanas

❮ Previous
Next ❯

Related Concepts

Related Feeds

Alzheimer's Disease: APP

Amyloid precursor protein (APP) proteolysis is critical for the development of Alzheimer's disease, a neurodegenerative disease associated with accumulation of amyloid plaques in the brain. Here is the latest research on APP and Alzheimer's disease.

Alzheimer's Disease: Amyloid Beta

Alzheimer's disease is a neurodegenerative disease associated with the accumulation of amyloid plaques in the brain; these plaques are comprised of amyloid beta deposits. Here is the latest research in this field.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis