Estradiol protects against beta-amyloid (25-35)-induced toxicity in SK-N-SH human neuroblastoma cells.

Abstract

Estrogen-replacement therapy has been associated with a reduced incidence of Alzheimer's disease (AD) and improved cognition in several small open clinical trials. We assessed the possibility that estrogens may reduce toxicity of beta-amyloid (A beta) by testing the effects of beta-estradiol on the toxicity of the neurotoxic fragment of beta-amyloid (A beta 25-35) in SK-N-SH neuroblastoma cells. A beta 25-35 caused a dose-dependent death in SK-N-SH cells with a LD50 of 28.9 muM. In cultures simultaneously exposed to 20 muM A beta and 17 beta-estradiol (2 nM). A beta-induced toxicity was reduced by 83 and 51% in two separate studies. Further studies show that 0.2 nM 17 beta-estradiol was as effective as the 2 nM concentration. 17 alpha-Estradiol (2 nM) conferred neuroprotection equivalent to that of 17 beta-estradiol. These data support the hypothesis that estrogens reduce beta-amyloid toxicity and this may help explain the beneficial effects of estrogens in AD.

• Authors: P S Green, K E Gridley, J W Simpkins
• Journal: Neuroscience letters (Neurosci Lett) Vol. 218 Issue 3 Pg. 165-8 (Nov 08 1996) ISSN: 0304-3940 [Print] Ireland
• PMID: 8945754 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Amyloid beta-Peptides
• Neuroprotective Agents
• Neurotoxins
• Peptide Fragments
• amyloid beta-protein (25-35)
• Estradiol

Topics

• Amyloid beta-Peptides (toxicity)
• Cell Survival (drug effects)
• Dose-Response Relationship, Drug
• Estradiol (pharmacology)
• Humans
• Neuroblastoma
• Neuroprotective Agents (pharmacology)
• Neurotoxins (pharmacology)
• Peptide Fragments (toxicity)
• Tumor Cells, Cultured (cytology, drug effects)