ArticleProceedings of the National Academy of Sciences of the United States of America2002
Testosterone prevents the heat shock-induced overactivation of glycogen synthase kinase-3 beta but not of cyclin-dependent kinase 5 and c-Jun NH2-terminal kinase and concomitantly abolishes hyperphosphorylation of tau: implications for Alzheimer's disease.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 99 citations in OpenAlex.
- Defining patient-centered amyloid PET thresholds for the onset of tauopathy in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Androgens Regulate Tau Phosphorylation Through Phosphatidylinositol 3-Kinase-Protein Kinase B-Glycogen Synthase Kinase 3β Signaling.Neuroscience · 2025Article
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- Low testosterone levels relate to poorer cognitive function in women in an APOE-ε4-dependant manner.Biology of sex differences · 2024Article
- Sex steroid and cognitive function among community-dwelling older men with or without vascular risk factors: a cross-sectional study.BMC geriatrics · 2024Article
- Salivary Testosterone and Cortisol Levels in Tunisian Elderly Male Patients With Mild Alzheimer's Disease. Implications of Musical Therapy And/Or Physical Rehabilitation.Frontiers in physiology · 2022Article
- Effects of Long-Acting Testosterone Undecanoate on Behavioral Parameters and Na + , KNeurochemical research · 2021Article
- In Vitro and In Vivo Evaluation of GSK-3 Radioligands in Alzheimer's Disease: Preliminary Evidence of Sex Differences.ACS pharmacology & translational science · 2021Article
- Sex Hormone Depletion Augments Glucocorticoid Induction of Tau Hyperphosphorylation in Male Rat Brain.Neuroscience · 2021Article
- Lower Plasma Total Testosterone Levels Were Associated With Steeper Decline in Brain Glucose Metabolism in Non-demented Older Men.Frontiers in aging neuroscience · 2021Article
- Risk of dementia following androgen deprivation therapy for treatment of prostate cancer.Prostate cancer and prostatic diseases · 2020Article
- Sex differences in Alzheimer's-related Tau biomarkers and a mediating effect of testosterone.Biology of sex differences · 2020Article
- Testosterone and Adult Neurogenesis.Biomolecules · 2020Review
- Chronological Molecular Changes in Neuronal Communication in Androgen-Deficient Rats.Journal of molecular neuroscience : MN · 2019Article
- Supraphysiologic-dose anabolic-androgenic steroid use: A risk factor for dementia?Neuroscience and biobehavioral reviews · 2019Review
- PQQ ameliorates D-galactose induced cognitive impairments by reducing glutamate neurotoxicity via the GSK-3β/Akt signaling pathway in mouse.Scientific reports · 2018Article
- Interactive effects of testosterone and cortisol on hippocampal volume and episodic memory in middle-aged men.Psychoneuroendocrinology · 2018Article
- Multiple Mechanisms Linking Type 2 Diabetes and Alzheimer's Disease: Testosterone as a Modifier.Journal of Alzheimer's disease : JAD · 2017Review
- Using redescription mining to relate clinical and biological characteristics of cognitively impaired and Alzheimer's disease patients.PloS one · 2017Article
- Endogenous sex hormones and cognitive function in older women.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2016Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We have shown previously that glycogen synthase kinase-3 beta (GSK-3 beta), cyclin-dependent kinase 5, and c-Jun NH(2)-terminal kinase become overactivated and hyperphosphorylate tau in heat-shocked female rats. This hyperphosphorylation of tau is estrogen-independent, prevented by androgens, and similar to Alzheimer's disease. In this study, ovariectomized (OVX) Sprague-Dawley rats (n = 75) received daily injections of 10 microg of 17 beta-estradiol benzoate (EB), or 250 microg of testosterone propionate (TP), or both EB and TP, or sesame oil (SO) vehicle for 4-6 weeks. In kinase assays of forebrain homogenates, overactivation of GSK-3 beta at 0-6 h after heat shock toward human recombinant tau, bovine tau, and phosphoglycogen synthase peptide 2 was prevented in OVX + TP and OVX + (EB + TP) but not in sham-OVX + SO, OVX + SO, and OVX + EB. Abs against inactive (pSer(9)) and activity-enhanced (pTyr(216)) GSK-3 beta showed marked increase of pSer(9)- and decrease of pTyr(216)-GSK-3 beta in both OVX + TP and OVX + (EB + TP) but not in sham-OVX + SO, OVX + SO, and OVX + EB. EB enhanced the overactivation of cyclin-dependent kinase 5. The activity of c-Jun NH(2)-terminal kinase was gonadal hormone-independent. The serum concentrations of testosterone and 17 beta-estradiol were 2.53 ng/ml and 201 pg/ml in OVX + TP and OVX + EB, respectively. These findings demonstrate that testosterone prevents the hyperphosphorylation of tau by inhibiting the heat shock-induced overactivation of GSK-3 beta and suggest that androgens given to aging men or, in combination with estrogens, to postmenopausal women could prevent or delay Alzheimer's disease.
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