Browsing by Subject "Heparan sulfate mimetic"

Now showing 1 - 2 of 2

Open Access
Cooperative effect of heparan sulfate and laminin mimetic peptide nanofibers on the promotion of neurite outgrowth
(Elsevier, 2012) Mammadov, Busra; Mammadov, Rashad; Güler, Mustafa O.; Tekinay, Ayse B.
Extracellular matrix contains an abundant variety of signals that are received by cell surface receptors contributing to cell fate, via regulation of cellular activities such as proliferation, migration and differentiation. Cues from extracellular matrix can be used for the development of materials to direct cells into their desired fate. Neural extracellular matrix (ECM) is rich in axonal growth inducer proteins, and by mimicking these permissive elements in the cellular environment, neural differentiation as well as neurite outgrowth can be induced. In this paper, we used a synthetic peptide nanofiber system that can mimic not only the activity of laminin, an axonal growth-promoting constituent of the neural ECM, but also the activity of heparan sulfate proteoglycans in order to induce neuritogenesis. Heparan sulfate mimetic groups that were utilized in our system have an affinity to growth factors and induce the neuroregenerative effect of laminin mimetic peptide nanofibers. The self-assembled peptide nanofibers with heparan sulfate mimetic and laminin-derived epitopes significantly promoted neurite outgrowth by PC-12 cells. In addition, these scaffolds were even effective in the presence of chondroitin sulfate proteoglycans (CSPGs), which are the major inhibitory components of the central nervous system. In the presence of these nanofibers, cells could overcome CSPG inhibitory effect and extend neurites on peptide nanofiber scaffolds. © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Open Access
Regenerative effects of peptide nanofibers in an experimental model of Parkinson's disease
(Elsevier Ltd, 2016) Sever, M.; Turkyilmaz, M.; Sevinc, C.; Cakir, A.; Ocalan, B.; Cansev, M.; Güler, Mustafa O.; Tekinay, A. B.
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-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.