Regenerative Effects Of Peptide Nanofibers In An Experimental Model Of Parkinson'S Disease
| Autor: | Mehmet Cansev, Melike Sever, Mesut Turkyilmaz, Mustafa O. Guler, Busra Ocalan, Aysen Cakir, Cansu Sevinc, Ayse B. Tekinay |
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| Přispěvatelé: | Güler, Mustafa O., Uludağ Üniversitesi/Tıp Fakültesi/Eczacılık Anabilim Dalı., Uludağ Üniversitesi/Tıp Fakültesi/Fizyoloji Anabilim Dalı., Türkyılmaz, Mesut, Sevinç, Cansu, Çakır, Aysen, Öcalan, Büşra, Cansev, Mehmet, A-6819-2018, M-9071-2019, N-9927-2019, AAL-1786-2020 |
| Rok vydání: | 2016 |
| Předmět: |
Male
Cell viability Parkinson's disease Nanofibers Heparan sulfate Apoptosis 6-hydroxydopamine Growth-factor Pharmacology Materials science biomaterials Biochemistry Rats Sprague-Dawley 0302 clinical medicine Recovery Cell Movement Pathology Amines Modulation Neurons Behavior Animal Parkinsonism Cell motion General Medicine Immunohistochemistry 3. Good health Protein secondary structure Microglia Human Tyrosine 3-Monooxygenase Calcium binding protein Biomedical Engineering Heparan sulphate Article Biomaterials 03 medical and health sciences Aif1 protein rat Humans Animal model Animal experiment Oxidopamine Molecular Biology Tyrosine hydroxylase Animal Disease model Calcium-Binding Proteins Amphiphiles Tumor cell line medicine.disease Materials science Engineering biomedical Nanostructures Nerve Regeneration Tyrosine 3 monooxygenase 030104 developmental biology Circling behavior Rat Laminin Peptides 030217 neurology & neurosurgery 0301 basic medicine Dopamine Biomimetic materials Striatum Protein Structure Secondary Experimental parkinsonism Engineering Biomimetics Heparan sulfate mimetic Forelimb Peptide amphiphiles Sulfur compounds Heparan sulphate mimetic Priority journal Caspase 3 Circular Dichroism Neurodegenerative diseases Microfilament Proteins Dopaminergic Parkinson Disease Extracellular matrix Nanomaterial Chemistry Sprague dawley rat Peptide Rat model Amino acids Akinesia 6-ohda Amphophile Scanning electron microscopy 6-Hydroxydopamine Animal behavior Biotechnology medicine.drug Levodopa Cell Survival Laminin mimetic Cell loss Reversed phase high performance liquid chromatography Neurochemical Cell Line Tumor medicine Animals Pathways Mimetics Drug effects Dexamphetamine Nanofiber Actin binding protein Nonhuman Corpus Striatum Rats Disease Models Animal Metabolism Heparan-sulfate Controlled study |
| Zdroj: | Acta Biomaterialia |
| Popis: | Parkinson'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-SYSY 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. Türkiye Bilimler Akademisi |
| Databáze: | OpenAIRE |
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