title: Neurorestorative effect of FTY720 in a rat model of Alzheimer's disease: comparison with memantine.
abstract: Alzheimer's disease (AD) as a neurodegenerative brain disorder is the most common cause of dementia. To date, there is no causative treatment for AD and there are few preventive treatments either. The sphingosine-1-phosphate receptor modulator FTY720 (fingolimod) prevents lymphocytes from contributing to an autoimmune reaction and has been approved for multiple sclerosis treatment. In concert with other studies showing the anti-inflammatory and protective effect of FTY720 in some neurodegenerative disorders like ischemia, we have recently shown that FTY720 chronic administration prevents from impairment of spatial learning and memory in AD rats. Here FTY720 was examined on AD rats in comparison to the only clinically approved NMDA receptor antagonist, Memantine. Passive avoidance task showed significant memory restoration in AD animals received FTY720 comparable to Memantine. Upon gene profiling by QuantiGene Plex, this behavioral outcomes was concurrent with considerable alterations in some genes transcripts like that of mitogen activated protein kinases (MAPKs) and some inflammatory markers that may particularly account for the detected decline in hippocampal neural damage or memory impairment associated with AD. From a therapeutic standpoint, our findings conclude that FTY720 may suggest new opportunities for AD management probably based on several modulatory effects on genes involved in cell death or survival.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Hemmati
authors.forename: Leila
authors.initials: L
authors.lastname: Dargahi
authors.forename: Sanaz
authors.initials: S
authors.lastname: Nasoohi
authors.forename: Rana
authors.initials: R
authors.lastname: Omidbakhsh
authors.forename: Zahurin
authors.initials: Z
authors.lastname: Mohamed
authors.forename: Zamri
authors.initials: Z
authors.lastname: Chik
authors.forename: Murali
authors.initials: M
authors.lastname: Naidu
authors.forename: Abolhassan
authors.initials: A
authors.lastname: Ahmadiani
mesh_terms: D000544:Alzheimer Disease / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D016229:Amyloid beta-Peptides / Q000633:toxicity; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D000068876:Fingolimod Hydrochloride; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000473:pathology; D008297:Male; D008559:Memantine / Q000627:therapeutic use*; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D009410:Nerve Degeneration / Q000139:chemically induced / Q000517:prevention & control; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000633:toxicity; D011409:Propylene Glycols / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D016229:Amyloid beta-Peptides; D016207:Cytokines; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D011409:Propylene Glycols; C075222:amyloid beta-protein (1-42); D020928:Mitogen-Activated Protein Kinases; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine; D008559:Memantine
keywords: Alzheimer's disease; FTY720; Gene profiling; Memantine; Sphingosine-1-phosphate