title: Neuroprotective effects of estrogens: the role of cholesterol.
abstract: BACKGROUND
  Experimental and clinical evidence suggests that estrogens have protective effects in the brain. Nevertheless, their potential role against neurodegenerative diseases, in particular Alzheimer's disease (AD), is still a matter of debate. The identification of the seladin-1 gene (for SELective Alzheimer's Disease INdicator-1), which appeared to be significantly less expressed in brain region affected in AD, opened a new scenario in the field of neuroprotective mechanisms. Seladin-1 was found to have neuroprotective properties through its anti-apoptotic activity. In addition, it was subsequently demonstrated that seladin-1 also has enzymatic activity, because it catalyzes the conversion of desmosterol into cholesterol. Several studies have shown that an appropriate amount of membrane cholesterol plays a pivotal role to protect nerve cells against β-amyloid toxicity in AD and to counteract the synthesis of β-amyloid.
  
  
  RESULTS
  We demonstrated that the expression of seladin-1, as well as the synthesis of cell cholesterol, is stimulated by estrogens in human neuronal precursor cells. Cholesterol enriched cells became more resistant against oxidative stress and β-amyloid toxicity. We thus hypothesized that seladin-1 might be a mediator of the neuroprotective effects of estrogens. Indeed, in cells in which seladin-1 gene expression had been silenced by siRNA the protective effects of estrogens were lost. This finding indicates that seladin-1 is a crucial mediator of the neuroprotective effects of these hormones, at least in our cell model.
  
  
  CONCLUSIONS
  In summary, these results establish a new link between estrogens and cholesterol, which is represented by the neuroprotective factor seladin-1.
authors.affiliation: Endocrine Unit, Department of Experimental and Biomedical Sciences "Mario Serio", Center for Research, Transfer and High Education on Chronic, Inflammatory, Degenerative and Neoplastic Disorders for the Development of Novel Therapies, University of Florence, Viale Pieraccini, 6, 50139, Florence, Italy. alessandro.peri@unifi.it.
authors.forename: A
authors.initials: A
authors.lastname: Peri
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002784:Cholesterol / Q000502:physiology*; D004967:Estrogens / Q000494:pharmacology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000502:physiology; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology
chemical_list: D004967:Estrogens; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D020845:Selective Estrogen Receptor Modulators; D007334:Insulin-Like Growth Factor I; D002784:Cholesterol; D044925:Oxidoreductases Acting on CH-CH Group Donors; C499055:DHCR24 protein, human
keywords: Alzheimer‘s disease; Cholesterol; DHCR24; Estrogens; Seladin-1