AR x TAU

Last update 23 Jan 2025

Basic Info

Related Targets

ARTAU

Drugs associated with AR x TAU

ADEL-Y07

Target

AR x TAU

Mechanism

AR antagonists [+1]

Active Org.

ADEL, Inc.

Originator Org.

ADEL, Inc.

Active Indication

Alzheimer Disease [+1]

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with AR x TAU

100 Translational Medicine associated with AR x TAU

0 Patents (Medical) associated with AR x TAU

Literatures (Medical) associated with AR x TAU

01 Mar 2025·Neuropharmacology

Neuroprotective effects of testosterone on sevoflurane-induced neurotoxicity in testosterone-deprived male mice

Article

Author: Long, Siwen ; Li, Dujuan ; Gong, Bingqing ; Li, Feixiang ; Yu, Jiafeng ; Yang, Yue ; Yang, Yongyan ; Yu, Yonghao

This study aims to investigate whether androgen deprivation, simulating conditions of aging or disease-induced low testosterone levels, increases the susceptibility of male mice to sevoflurane neurotoxicity, and whether testosterone supplementation can reverse the toxic effects of sevoflurane. In here, young male mice were subjected to orchiectomy (ORC) to induce testosterone deprivation. Various techniques, including western blotting, immunofluorescence, Morris Water Maze, Golgi staining, and neuronal signal measurement, were used to evaluate the effects of sevoflurane on long-term (ORC 10 weeks) and short-term (ORC 2 weeks) testosterone deprivation, and assess whether testosterone (1 mg/kg 1 h before sevoflurane exposure) could mitigate sevoflurane-induced neurotoxicity. Flutamide and anastrozole were administered to study testosterone's pathways of action. We found that sevoflurane increased tau phosphorylation and decreased the transient amplitude of Ca²⁺ signals and dendritic spine density in dorsal hippocampal CA1 (dCA1) neurons, leading to cognitive impairment in testosterone-deprived male mice. Testosterone treatment reversed the effects of sevoflurane in short-term testosterone-deprived male mice, but not in long-term testosterone-deprived male mice. Additionally, the neuroprotective effect of testosterone was blocked by flutamide rather than anastrozole. We have discovered for the first time that testosterone can mitigate the sevoflurane-induced neurotoxicity in testosterone-deprived male mice and that there exists a therapeutic time window, which may be mediated by androgen receptors. This may provide new insights into the neuroprotective role of sex hormones.

01 Dec 2024·Alzheimer's & Dementia

Androgen receptor upregulation regulates tau pathology in a female tauopathy mouse model

Article

Author: Lyu, Xinchen ; Rissman, Robert A. ; Chen, Xu ; Kauffman, Alexander S. ; Munoz‐Mayorga, Daniel ; Tao, Yuren

AbstractBackgroundAccording to data from the Alzheimer’s Association, more than two‐thirds of patients living with Alzheimer’s disease (AD) in the United States are women. The interplay between aging and hormone depletion during menopause has been proposed as a leading cause, but the molecular underpinnings of this vulnerability are not fully understood. On the one hand, approaches that seek to supplement estrogens to rescue pre‐menopausal hormonal levels have had contradictory outcomes in clinical trials. On the other hand, androgen effects in women in a neurodegeneration context are dramatically understudied. Furthermore, the number of XX chromosome individuals using androgens for sex‐reassignment purposes has steadily increased. Whether androgens can regulate tau pathology and how is poorly understood, especially in the context of female physiology.MethodWe performed a dihydrotestosterone (DHT) supplementation paradigm in 5‐6 month old P301S female mice and harvested brain tissue at 9 months of age. Pathological and biochemical tau markers, as well as androgen receptor content were evaluated in the hippocampus and cortex.ResultHere, we report an exacerbation of tau pathology in tauP301S female mice treated with DHT, an androgen receptor (AR)‐specific ligand, in the hippocampus, as evaluated by AT8 and MC‐1 immunostaining. Furthermore, we report upregulation of AR almost exclusively in neurons upon DHT treatment, potentially mediating our observations.ConclusionOur results implicate AR activation in females as a potential risk factor for tau pathology. Overall, the AD field will benefit from a more thorough understanding of neurodegeneration in women and transmasculine individuals, facilitating the identification of different risk and protection factor, paving the way to the development of novel and targeted therapies, and better addressing the health issues of our diverse society.

06 Nov 2024·Clinical Science

Untangling the role of tau in sex hormone responsive cancers: lessons learnt from Alzheimer's disease

Review

Author: Barker, Rachel M. ; Kehoe, Patrick G. ; Rowe, Edward ; Perks, Claire M. ; Chambers, Alfie

AbstractTubulin associated unit has been extensively studied in neurodegenerative diseases including Alzheimer's disease (AD), whereby its hyperphosphorylation and accumulation contributes to disease pathogenesis. Tau is abundantly expressed in the central nervous system but is also present in non-neuronal tissues and in tumours including sex hormone responsive cancers such as breast and prostate. Curiously, hormonal effects on tau also exist in an AD context from numerous studies on menopause, hormone replacement therapy, and androgen deprivation therapy. Despite sharing some risk factors, most importantly advancing age, there are numerous reports from population studies of, currently poorly explained inverse associations between cancer and Alzheimer's disease. We previously reviewed important components of the phosphoinositide-3-kinase/protein kinase B (PI3K/Akt) signalling pathway and their differential modulation in relation to the two diseases. Similarly, receptor tyrosine kinases, estrogen receptor and androgen receptor have all been implicated in the pathogenesis of both cancer and AD. In this review, we focus on tau and its effects in hormone responsive cancer in terms of development, progression, and treatment and in relation to sex hormones and PI3K/Akt signalling molecules including IRS-1, PTEN, Pin1, and p53.

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