Role of the androgen receptor in the central nervous system

Mhaouty-Kodja, Sakina

doi:10.1016/j.mce.2017.08.001

Cited by 62 publications

(54 citation statements)

References 125 publications

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“…In adult rodents, AR mRNA and protein are detected in neurons and glia of the medial amygdala, the preoptic area, the hypothalamus, the cerebellum, and the dentate gyrus of the hippocampus (Commins and Yahr, 1985 ; Sar et al, 1990 ; Hajszan et al, 2007 ; Feng et al, 2010 ; Pelletier, 2010 ; Mhaouty-Kodja, 2017 ). Interestingly, AR protein level is correlated with circulating levels of estradiol and testosterone across the estrous cycle, suggesting an estrogenic regulation of its expression (Feng et al, 2010 ).…”

Section: Steroid Signaling In the Brain: Focus On The Brains Of Fishmentioning

confidence: 99%

Steroid Transport, Local Synthesis, and Signaling within the Brain: Roles in Neurogenesis, Neuroprotection, and Sexual Behaviors

et al. 2018

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Sex steroid hormones are synthesized from cholesterol and exert pleiotropic effects notably in the central nervous system. Pioneering studies from Baulieu and colleagues have suggested that steroids are also locally-synthesized in the brain. Such steroids, called neurosteroids, can rapidly modulate neuronal excitability and functions, brain plasticity, and behavior. Accumulating data obtained on a wide variety of species demonstrate that neurosteroidogenesis is an evolutionary conserved feature across fish, birds, and mammals. In this review, we will first document neurosteroidogenesis and steroid signaling for estrogens, progestagens, and androgens in the brain of teleost fish, birds, and mammals. We will next consider the effects of sex steroids in homeostatic and regenerative neurogenesis, in neuroprotection, and in sexual behaviors. In a last part, we will discuss the transport of steroids and lipoproteins from the periphery within the brain (and vice-versa) and document their effects on the blood-brain barrier (BBB) permeability and on neuroprotection. We will emphasize the potential interaction between lipoproteins and sex steroids, addressing the beneficial effects of steroids and lipoproteins, particularly HDL-cholesterol, against the breakdown of the BBB reported to occur during brain ischemic stroke. We will consequently highlight the potential anti-inflammatory, anti-oxidant, and neuroprotective properties of sex steroid and lipoproteins, these latest improving cholesterol and steroid ester transport within the brain after insults.

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Section: Steroid Signaling In the Brain: Focus On The Brains Of Fishmentioning

confidence: 99%

Steroid Transport, Local Synthesis, and Signaling within the Brain: Roles in Neurogenesis, Neuroprotection, and Sexual Behaviors

et al. 2018

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“…The androgen receptor (AR) is similar in structure to the PRs, with a variable N-terminal transcriptional regulation domain, conserved DNA binding domain, and ligand binding domain (Mhaouty-Kodja, 2017 ). Also like PR, in the absence of hormones, the AR is complexed with chaperones in the cytosol.…”

Section: Sex Hormones and Receptors In The Cnsmentioning

confidence: 99%

Sex Differences in Autophagy Contribute to Female Vulnerability in Alzheimer's Disease

Congdon

2018

Front. Neurosci.

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Alzheimer's disease (AD) is the most common form of dementia, with over 5. 4 million cases in the US alone (Alzheimer's Association, 2016). Clinically, AD is defined by the presence of plaques composed of Aβ and neurofibrillary pathology composed of the microtubule associated protein tau. Another key feature is the dysregulation of autophagy at key steps in the pathway. In AD, disrupted autophagy contributes to disease progression through the failure to clear pathological protein aggregates, insulin resistance, and its role in the synthesis of Aβ. Like many psychiatric and neurodegenerative diseases, the risk of developing AD, and disease course are dependent on the sex of the patient. One potential mechanism through which these differences occur, is the effects of sex hormones on autophagy. In women, the loss of hormones with menopause presents both a risk factor for developing AD, and an obvious example of where sex differences in AD can stem from. However, because AD pathology can begin decades before menopause, this does not provide the full answer. We propose that sex-based differences in autophagy regulation during the lifespan contribute to the increased risk of AD, and greater severity of pathology seen in women.

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“…Some studies have suggested that peripheral knockdown of the AR is sufficient to rescue disease phenotypes in SBMA mouse models [8,169]. Should these findings translate to patients, it would simplify drug delivery and spare androgen receptor function in the CNS [222]. However, there is also evidence that expression of the AR in the CNS drives disease [178,218].…”

Section: Sbma-open Questionsmentioning

confidence: 99%

Molecular Mechanisms and Therapeutics for SBMA/Kennedy's Disease

Arnold

Merry

2019

Neurotherapeutics

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Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular disease caused by a polyglutamine (polyQ) expansion in the androgen receptor (AR). Despite the fact that the monogenic cause of SBMA has been known for nearly 3 decades, there is no effective treatment for this disease, underscoring the complexity of the pathogenic mechanisms that lead to a loss of motor neurons and muscle in SBMA patients. In the current review, we provide an overview of the system-wide clinical features of SBMA, summarize the structure and function of the AR, discuss both gain-of-function and loss-of-function mechanisms of toxicity caused by polyQ-expanded AR, and describe the cell and animal models utilized in the study of SBMA. Additionally, we summarize previously conducted clinical trials which, despite being based on positive results from preclinical studies, proved to be largely ineffective in the treatment of SBMA; nonetheless, these studies provide important insights as researchers develop the next generation of therapies.

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Role of the androgen receptor in the central nervous system

Cited by 62 publications

References 125 publications

Steroid Transport, Local Synthesis, and Signaling within the Brain: Roles in Neurogenesis, Neuroprotection, and Sexual Behaviors

Steroid Transport, Local Synthesis, and Signaling within the Brain: Roles in Neurogenesis, Neuroprotection, and Sexual Behaviors

Sex Differences in Autophagy Contribute to Female Vulnerability in Alzheimer's Disease

Molecular Mechanisms and Therapeutics for SBMA/Kennedy's Disease

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