New insights on the neuroprotective role of sterols and sex steroids: The seladin-1/DHCR24 paradigm

• Published in: Frontiers in neuroendocrinology Vol. 30; no. 2; pp. 119 - 129
• Main Authors: Peri, Alessandro, Danza, Giovanna, Benvenuti, Susanna, Luciani, Paola, Deledda, Cristiana, Rosati, Fabiana, Cellai, Ilaria, Serio, Mario
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2009
• Subjects: Alzheimer’s disease; Animals; Brain; Cholesterol; Cholesterol - chemistry; Cholesterol - metabolism; DHCR24; Endocrinology & Metabolism; Estrogens; Estrogens - chemistry; Estrogens - metabolism; Humans; Molecular Structure; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Neuroblast; Neurodegeneration; Neurodegenerative Diseases - metabolism; Neurodegenerative Diseases - pathology; Neurodegenerative Diseases - therapy; Neuroprotective Agents - metabolism; Oxidoreductases Acting on CH-CH Group Donors - genetics; Oxidoreductases Acting on CH-CH Group Donors - metabolism; Plant Proteins - genetics; Plant Proteins - metabolism; Seladin-1; Brain; Alzheimer’s disease; Neurodegeneration; Seladin-1; Estrogens; DHCR24; Neuroblast; Cholesterol
• ISSN: 0091-3022; 1095-6808
• DOI: 10.1016/j.yfrne.2009.03.006

Abstract In 2000 a new gene, i.e. seladin-1 (for selective Alzheimer’s disease indicator-1) was identified and found to be down regulated in vulnerable brain regions in Alzheimer’s disease. Seladin-1 was considered a novel neuroprotective factor, because of its anti-apoptotic properties. Subsequently, it has been demonstrated that seladin-1 corresponds to the gene that encodes 3-beta-hydroxysterol delta-24-reductase ( DHCR24 ), that catalyzes the synthesis of cholesterol from desmosterol. There is evidence that cholesterol plays a fundamental role in maintaining brain homeostasis. Because of its enzymatic activity, seladin-1/DHCR24 has been considered the human homolog of the plant protein DIMINUTO/DWARF1, that is involved in the synthesis of sterol plant hormones. We have recently demonstrated that seladin-1/DHCR24 is a fundamental mediator of the protective effects of estrogens in the brain. This review describes how this protein interacts with cholesterol and estrogens, thus generating a neuroprotective network, that might open new possibilities in the prevention/treatment of neurodegenerative diseases.