ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2004
Estrogen and androgen protection of human neurons against intracellular amyloid beta1-42 toxicity through heat shock protein 70.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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61 citing papers in PubMed, 136 citations in OpenAlex.
- Anti-aging effects of the adrenal androgens dehydroepiandrosterone and dehydroepiandrosterone sulfate: mechanisms of action and beneficial effects in older people.Endocrine journal · 2026Review
- Beyond Estrogen: Unraveling the Complexities of Hormonal Signaling Pathways in Alzheimer's Disease and Their Implications for Precision Therapy.Molecular neurobiology · 2025Review
- Dietary Choline Intake and Risk of Alzheimer's Dementia in Older Adults.The Journal of nutrition · 2025Article
- Causal effects of genetically predicted testosterone on Alzheimer's disease: a two-sample mendelian randomization study.Acta neurologica Belgica · 2024Article
- Testosterone Inhibits Secretion of the Pro-Inflammatory Chemokine CXCL1 from Astrocytes.Current issues in molecular biology · 2024Article
- Sex-based differences in effector cells of the adaptive immune system during Alzheimer's disease and related dementias.Neurobiology of disease · 2023Review
- Sex-dependent metal accumulation and immunoexpression of Hsp70 and Nrf2 in rats' brain following manganese exposure.Environmental toxicology · 2022Article
- [Testosterone and Alzheimer's disease].Problemy endokrinologii · 2022Article
- Impact of Testosterone on Alzheimer's Disease.The world journal of men's health · 2022Review
- Deficiency in Androgen Receptor Aggravates Traumatic Brain Injury-Induced Pathophysiology and Motor Deficits in Mice.Molecules (Basel, Switzerland) · 2021Article
- From Menopause to Neurodegeneration-Molecular Basis and Potential Therapy.International journal of molecular sciences · 2021Review
- Sex differences in fat taste responsiveness are modulated by estradiol.American journal of physiology. Endocrinology and metabolism · 2021Article
- Testosterone Deficiency and Risk of Cognitive Disorders in Aging Males.The world journal of men's health · 2021Review
- Androgen Therapy in Neurodegenerative Diseases.Journal of the Endocrine Society · 2020Review
- Testosterone Levels Are Decreased and Associated with Disease Duration in Male Spinocerebellar Ataxia Type 2 Patients.Cerebellum (London, England) · 2020Article
- Testosterone and Adult Neurogenesis.Biomolecules · 2020Review
- An Updated Review: Androgens and Cognitive Impairment in Older Men.Frontiers in endocrinology · 2020Review
- Neuroprotective Effects of Exercise on the Morphology of Somatic Motoneurons Following the Death of Neighboring Motoneurons.Neurorehabilitation and neural repair · 2019Article
- Neuroprotective Effects on the Morphology of Somatic Motoneurons Following the Death of Neighboring Motoneurons: A Role for Microglia?Developmental neurobiology · 2019Article
- Estrogen and estrogen receptors in the modulation of gastrointestinal epithelial secretion.Oncotarget · 2017Review
1 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Intracellular amyloidbeta peptide (iAbeta1-42) accumulates in the Alzheimer's disease brain before plaque and tangle formation (Gouras et al., 2000) and is extremely toxic to human neurons (Zhang et al., 2002). Here, we investigated whether androgen and estrogen could prevent iAbeta1-4) toxicity, because both these hormones have a wide range of neuroprotective actions. At physiological concentrations, 17-beta-estradiol, testosterone, and methyl testosterone reduce iAbeta1-42-induced cell death by 50% in neurons treated after the injection and by 80-90% in neurons treated 1 hr before the injection. The neuroprotective action of the hormones is mediated by receptors, because the estrogen receptor (ER) antagonist tamoxifen and the androgen receptor (AR) antagonist flutamide completely block the estrogen- and androgen-mediated neuroprotection, respectively. Transcriptional activity is required for the neuroprotective action, because dominant negative forms of the receptors that block the transcriptional activity of the ER and AR prevent estrogen- and androgen-mediated neuroprotection. Proteomics followed by Western blot analyses identified increased levels of heat shock protein 70 (Hsp70) in testosterone- and estrogen-treated human neurons. Comicroinjection of Hsp70 with the iAbeta1-42 blocks the toxicity of iAbeta1-42. We conclude that estrogen and androgens protect human neurons against iAbeta1-42 toxicity by increasing the levels of Hsp70 in the neurons.
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