Therapeautic effects of FTY720 compounds in cellular and animal models of multiple system atrophy

dc.contributor.committeeChairBergeson, Susan
dc.contributor.committeeMemberLakshmanaswamy, Rajkumar
dc.contributor.committeeMemberBlanton, Michael P.
dc.contributor.committeeMemberO'Dell, Laura E.
dc.creatorSegura-Ulate, Ismael
dc.date.accessioned2023-02-03T17:46:27Z
dc.date.available2023-02-03T17:46:27Z
dc.date.issued2018-05
dc.description.abstractMultiple system atrophy (MSA) is a rapidly progressing and fatal demyelinating neurodegenerative disorder with no effective treatment. MSA is characterized by the toxic accumulation of the protein alpha-synuclein (aSyn) inside oligodendroglia (OLG), the myelinating cells of the brain. We corroborated reports that aSyn accumulation inside OLG cells decreases expression of brain-derived neurotrophic factor (BDNF), a potent neuroprotective molecule. We further found that treating OLG cells with FTY720, an FDA-approved immunosuppressant drug, counteracts aSyn-induced BDNF downregulation in the cells. We then studied an FTY720 analogue, FTY720-Mitoxy, created by Drs. Perez and Arterburn. We found that FTY720-Mitoxy is not immunosuppressive. Moreover, FTY720-Mitoxy increased expression of BDNF and glial-cell line derived neurotrophic factor (GDNF) in OLG cells, trophic factors that are both downregulated in MSA brains. Furthermore, FTY720-Mitoxy increase GDNF expression in a transgenic mouse model of MSA while also reversing motor dysfunction. Thus, both FTY720 and FTY720-Mitoxy represent promising therapeutic options for patients with MSA. A potential advantage of FTY720-Mitoxy is its ability to increase GDNF expression without causing immunosuppression.en_US
dc.format.mimetypeapplication/pdf
dc.identifier.urihttps://hdl.handle.net/2346/90517
dc.language.isoengen_US
dc.rights.availabilityAccess is not restricted.
dc.subjectFTY720
dc.subjectMultiple system atrophy
dc.subjectneuroprotection
dc.titleTherapeautic effects of FTY720 compounds in cellular and animal models of multiple system atrophyen_US
dc.typeThesisen_US
dc.typetext
thesis.degree.departmentBiomedical Sciences
thesis.degree.disciplinePharmacology and Neuroscience
thesis.degree.grantorTexas Tech University Health Science Center
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Philosophy

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