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. 2009 Elsevier Inc. All rights reserved.
New insights on the neuroprotective role of sterols and sex steroids: the seladin-1/DHCR24 paradigm / A. Peri;G. Danza;S. Benvenuti;P. Luciani;C. Deledda;F. Rosati;I. Cellai;M. Serio. - In: FRONTIERS IN NEUROENDOCRINOLOGY. - ISSN 0091-3022. - STAMPA. - 30:(2009), pp. 119-129. [10.1016/j.yfrne.2009.03.006]
New insights on the neuroprotective role of sterols and sex steroids: the seladin-1/DHCR24 paradigm.
PERI, ALESSANDRO;DANZA, GIOVANNA;BENVENUTI, SUSANNA;LUCIANI, PAOLA;ROSATI, FABIANA;SERIO, MARIO
2009
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. 2009 Elsevier Inc. All rights reserved.File | Dimensione | Formato | |
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