New insights on the neuroprotective role of sterols and sex steroids: the seladin-1/DHCR24 paradigm.
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.
Peri
Alessandro
A
Department of Clinical Physiopathology, Endocrine Unit, Center for Research, University of Florence, Florence, Italy. a.peri@dfc.unifi.it
Danza
Giovanna
G
Benvenuti
Susanna
S
Luciani
Paola
P
Deledda
Cristiana
C
Rosati
Fabiana
F
Cellai
Ilaria
I
Serio
Mario
M
D000818:Animals; D002784:Cholesterol / Q000737:chemistry / Q000378:metabolism*; D004967:Estrogens / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D015394:Molecular Structure; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D018696:Neuroprotective Agents / Q000378:metabolism*; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000235:genetics / Q000378:metabolism*; D010940:Plant Proteins / Q000235:genetics / Q000378:metabolism
D004967:Estrogens; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D010940:Plant Proteins; D002784:Cholesterol; D044925:Oxidoreductases Acting on CH-CH Group Donors; C499055:DHCR24 protein, human