title: FTY720-derivatives do not induce FTY720-like lymphopenia.
abstract: FTY720 is an immunosuppressive multiple sclerosis (MS) drug that stimulates the expression of neuroprotective brain-derived-neurotrophic-factor (BDNF). In vivo preclinical data suggest that FTY720 could be beneficial for treating Parkinson's patients, though its immunosuppressive effects might limit its efficacy. Two novel FTY720-derivatives, FTY720-C2 and FTY720-Mitoxy, also stimulate BDNF expression and enter brain like FTY720 but are not phosphorylated, suggesting they will not produce FTY720-like immunosuppression. Using FTY720 as a positive control, we measured low and high dose FTY720-derivatives, which did not stimulate FTY720-like lymphopenia or immunosuppressive signaling. These findings support the further preclinical assessment of the derivatives as potential novel Parkinson's therapies.
authors.affiliation: Department of Biomedical Sciences, Graduate School of Biomedical Sciences, Center of Emphasis in Neurosciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX, United States.
authors.forename: Ismael
authors.initials: I
authors.lastname: Segura-Ulate
authors.affiliation: Department of Biomedical Sciences, Graduate School of Biomedical Sciences, Center of Emphasis in Neurosciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX, United States.
authors.forename: Troy K
authors.initials: TK
authors.lastname: Belcher
authors.affiliation: Department of Biomedical Sciences, Graduate School of Biomedical Sciences, Center of Emphasis in Neurosciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX, United States.
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Vidal-Martinez
authors.affiliation: Department of Biomedical Sciences, Graduate School of Biomedical Sciences, Center of Emphasis in Neurosciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX, United States.
authors.forename: Javier
authors.initials: J
authors.lastname: Vargas-Medrano
authors.affiliation: Department of Biomedical Sciences, Graduate School of Biomedical Sciences, Center of Emphasis in Neurosciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX, United States. Electronic address: ruth.g.perez@ttuhsc.edu.
authors.forename: Ruth G
authors.initials: RG
authors.lastname: Perez
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D007958:Leukocyte Count; D008214:Lymphocytes / Q000187:drug effects*; D008231:Lymphopenia; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000187:drug effects; D010766:Phosphorylation; D049349:Receptors, Lysosphingolipid / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000081025:Sphingosine-1-Phosphate Receptors
chemical_list: D049349:Receptors, Lysosphingolipid; C556330:S1pr1 protein, mouse; D000081025:Sphingosine-1-Phosphate Receptors; D013110:Sphingosine
keywords: Anti-inflammatory; Fingolimod; Neuroprotection