Estrogen Receptors: A New Frontier in Alzheimer's Disease Therapy

• Published in: International journal of molecular sciences Vol. 25; no. 16; p. 9077
• Main Authors: Cipriano, Giovanni Luca, Mazzon, Emanuela, Anchesi, Ivan
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 21-08-2024; MDPI
• Subjects: Aging; Alzheimer Disease - drug therapy; Alzheimer Disease - metabolism; Alzheimer’s disease; Amyloid beta-Protein Precursor - metabolism; Animals; Biomarkers; Dementia; Disease prevention; DNA methylation; Endocrine therapy; Epigenetics; estrogen receptors; estrogen signaling; Estrogens; Estrogens - metabolism; Health risk assessment; Humans; Kinases; Memory; Middle age; neurodegenerative diseases; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; Pathogenesis; Phosphatase; Phosphorylation; Physiology; Phytoestrogens - metabolism; Phytoestrogens - pharmacology; Phytoestrogens - therapeutic use; Plasmids; Polymerization; Receptors, Estrogen - metabolism; Review; Risk factors; Roles; Selective Estrogen Receptor Modulators - pharmacology; Selective Estrogen Receptor Modulators - therapeutic use; Signal transduction; Womens health; estrogen signaling; neurodegenerative diseases; Alzheimer’s disease; estrogen receptors
• ISSN: 1661-6596; 1422-0067; 1422-0067
• DOI: 10.3390/ijms25169077

Alzheimer's disease (AD) is a long-term neurodegenerative condition that leads to the deterioration of neurons and synapses in the cerebral cortex, resulting in severe dementia. AD is significantly more prevalent in postmenopausal women, suggesting a neuroprotective role for estrogen. Estrogen is now known to regulate a wide array of physiological functions in the body by interacting with three known estrogen receptors (ERs) and with the β-amyloid precursor protein, a key factor in AD pathogenesis. Recent experimental evidence indicates that new selective ER modulators and phytoestrogens may be promising treatments for AD for their neuroprotective and anti-apoptotic properties. These alternatives may offer fewer side effects compared to traditional hormone therapies, which are associated with risks such as cardiovascular diseases, cancer, and metabolic dysfunctions. This review sheds light on estrogen-based treatments that may help to partially prevent or control the neurodegenerative processes characteristic of AD, paving the way for further investigation in the development of estrogen-based treatments.