Steroidogenic acute regulatory protein mediated variations of gender-specific sex neurosteroids in Alzheimer's disease: Relevance to hormonal and neuronal imbalance

Pulak R Manna; Shengping Yang; Chayan Manna; Hope Waters; Islam Md Ariful; Arubala P Reddy; Priyanka Rawat; P Hemachandra Reddy

doi:10.1016/j.neubiorev.2024.105969

Steroidogenic acute regulatory protein mediated variations of gender-specific sex neurosteroids in Alzheimer's disease: Relevance to hormonal and neuronal imbalance

Neurosci Biobehav Rev. 2024 Dec 2:169:105969. doi: 10.1016/j.neubiorev.2024.105969. Online ahead of print.

Authors

Pulak R Manna¹, Shengping Yang², Chayan Manna³, Hope Waters⁴, Islam Md Ariful⁴, Arubala P Reddy⁵, Priyanka Rawat⁵, P Hemachandra Reddy⁶

Affiliations

¹ Department of Internal Medicine, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA. Electronic address: [email protected].
² Department of Biostatistics, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 70808, USA.
³ Baylor College of Medicine, Ben Taub Research Center, 1 Baylor Plaza, Houston, TX 77030, USA.
⁴ Department of Internal Medicine, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.
⁵ Nutritional Sciences Department, College of Human Sciences, Texas Tech University, Lubbock, TX 79409, USA.
⁶ Department of Internal Medicine, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA; Nutritional Sciences Department, College of Human Sciences, Texas Tech University, Lubbock, TX 79409, USA; Neurology, Departments of School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA; Public Health Department of Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA; Department of Speech, Language and Hearing Sciences, School Health Professions, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA; Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA. Electronic address: [email protected].

PMID: 39631487
DOI: 10.1016/j.neubiorev.2024.105969

Abstract

The steroidogenic acute regulatory (StAR) protein mediates the rate-liming step in neuro/steroid biosynthesis. Multifaceted and delicate changes during aging, disrupting hormonal and neuronal homeostasis, constitute human senescence, an inevitable phenomenon that attributes to increased morbidity and mortality. Aging, along with progressive decreases in bioactive neurosteroids, is the primary risk factor for Alzheimer's disease (AD), which preferentially impacts two-thirds of women and one-third of men. AD is neuropathologically characterized by the accumulation of extracellular amyloid-β and intracellular phosphorylated Tau containing neurofibrillary tangles, resulting in dementia. Postmortem brains pertaining to gender-specific AD patients exhibit varied suppression of StAR and sex neurosteroid levels compared with age-matched cognitively healthy subjects, in which the attenuation of StAR is inversely correlated with the AD pathological markers. Interestingly, retinoid signaling upregulates StAR-motivated neurosteroid biosynthesis and reinstates various neurodegenerative vulnerabilities that promote AD pathogenesis. This review summarizes current understanding of StAR-driven alterations of sex neurosteroids in gender-specific AD risks and provides biochemical and molecular insights into therapeutic interventions for preventing and/or alleviating dementia for healthy aging.

Keywords: Alzheimer’s disease (AD); Steroidogenic acute regulatory protein; aging; gender-specific differences in AD; neurosteroids; retinoid signaling.

Publication types

Review