Regenerative effects of peptide nanofibers in an experimental model of Parkinson's disease

buir.contributor.authorGüler, Mustafa O.
dc.citation.epage90en_US
dc.citation.spage79en_US
dc.citation.volumeNumber46en_US
dc.contributor.authorSever, M.en_US
dc.contributor.authorTurkyilmaz, M.en_US
dc.contributor.authorSevinc, C.en_US
dc.contributor.authorCakir, A.en_US
dc.contributor.authorOcalan, B.en_US
dc.contributor.authorCansev, M.en_US
dc.contributor.authorGüler, Mustafa O.en_US
dc.contributor.authorTekinay, A. B.en_US
dc.date.accessioned2018-04-12T10:56:27Z
dc.date.available2018-04-12T10:56:27Z
dc.date.issued2016en_US
dc.departmentInstitute of Materials Science and Nanotechnology (UNAM)en_US
dc.departmentNanotechnology Research Center (NANOTAM)en_US
dc.description.abstractParkinson's disease (PD) is characterized by progressive degeneration of dopaminergic nigrostriatal neurons and reduction in striatal dopamine levels. Although there are few treatment options for PD such as Levodopa, they are used just to relieve and modify the symptoms. There are no therapies available for PD to slow down the degeneration process in the brain and recover the lost function. In this study, we used extracellular matrix (ECM) mimetic peptide amphiphile (PA) nanofibers as a potential therapeutic approach in a PD rat model. We demonstrated the effect of heparan sulfate mimetic and laminin mimetic PA nanofibers on reducing striatal injury and enhancing functional recovery after unilateral striatal injection of 6-hydroxydopamine (6-OHDA). The bioactive self-assembled PA nanofibers significantly reduced forelimb asymmetry, contralateral forelimb akinesia and d-amphetamine-induced rotational behavior in cylinder, stepping and rotation tests, respectively, in 6-OHDA-lesioned rats after 6 weeks. The behavioral improvement with PA nanofiber administration was associated with enhanced striatal dopamine and tyrosine hydroxylase content as well as reduced cleaved-Caspase-3 levels. Histological assessment also showed that PA nanofiber injection to the striatum resulted in better tissue integrity compared to control groups. In addition, PA nanofibers reduced the progressive cell loss in SH-SY5Y cells caused by 6-OHDA treatment. These data showed that the bioactive peptide nanofibers improve neurochemical and behavioral consequences of Parkinsonism in rats and provide a promising new strategy for treatment of PD. Statement of Significance Biomimetic nanomaterials bearing natural bioactive signals which are derived from extracellular matrix components like laminin and heparan sulfates provide promising therapeutic strategies for regeneration of the nervous system. However, no research has been reported exploring the use of biomimetic materials against degeneration in Parkinson's disease. In this work, we investigated potential therapeutic effects of heparan sulfate and laminin mimetic PA nanofibers on reduction of striatal injury in experimental Parkinson's disease model. PA nanofibers enhanced functional recovery associated with enhanced striatal dopamine and tyrosine hydroxylase content as well as reduced cleaved-Caspase-3 levels. Overall, this study shows the improvement in consequences of Parkinsonism in rats and provides a new platform for treatment of Parkinson's disease. © 2016 Acta Materialia Inc.en_US
dc.description.provenanceMade available in DSpace on 2018-04-12T10:56:27Z (GMT). No. of bitstreams: 1 bilkent-research-paper.pdf: 179475 bytes, checksum: ea0bedeb05ac9ccfb983c327e155f0c2 (MD5) Previous issue date: 2016en
dc.identifier.doi10.1016/j.actbio.2016.09.011en_US
dc.identifier.issn1742-7061
dc.identifier.urihttp://hdl.handle.net/11693/36881
dc.language.isoEnglishen_US
dc.publisherElsevier Ltden_US
dc.relation.isversionofhttp://dx.doi.org/10.1016/j.actbio.2016.09.011en_US
dc.source.titleActa Biomaterialiaen_US
dc.subject6-Hydroxydopamineen_US
dc.subjectHeparan sulfate mimeticen_US
dc.subjectLaminin mimeticen_US
dc.subjectParkinson's diseaseen_US
dc.titleRegenerative effects of peptide nanofibers in an experimental model of Parkinson's diseaseen_US
dc.typeArticleen_US

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