Browsing by Subject "neurodegenerative disease"

Now showing 1 - 3 of 3
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    Adipose-derived stem cell conditioned medium for the treatment of amyotrophic lateral sclerosis: pre-clinical evidence and potential for clinical application
    (Medknow Publications, 2019-09) Walker, Chandler L.; Department of Biomedical and Applied Sciences, School of Dentistry
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    N-terminus of pro-EMAP II regulates its binding with C-terminus, Arginyl-tRNA Synthetase, and Neurofilament light protein
    (2015-04) Xu, Haiming; Malinin, Nikolay L.; Awasthi, Niranjan; Schwarz, Roderich E.; Schwarz, Margaret A.; Department of Pediatrics, Indiana University School of Medicine
    Pro-EMAP II, one component of the Multi-Aminoacyl tRNA Synthetase (MSC) Complex, plays multiple roles in physiological and pathological processes of protein translation, signal transduction, immunity, lung development and tumor growth. Recent studies determined that pro-EMAP II has an essential role in maintaining axon integrity in central and peripheral neural systems where deletion of pro-EMAP IIs C-terminus was reported in a consanguineous Israeli Bedouin kindred suffering from Pelizaeus-Merzbacher-like disease. We hypothesized that pro-EMAP IIs N-terminus had an important role in the regulation of protein-protein interactions. Using a GFP reporter system, we defined a putative leucine-zipper in the N-terminus of human pro-EMAP II protein (amino acid residues 1-70), which can form specific strip-like punctate structures. Through GFP punctate analysis, we uncovered that pro-EMAP IIs C-terminus (147-312 amino acid residues) can repress the GFP punctate formation. Pull-down assays confirmed the binding between pro-EMAP II N-terminus and its C-terminus is mediated by a putative leucine-zipper. Furthermore, the pro-EMAP II 1-70 aa region was identified as the binding partner of the arginyl-tRNA synthetase (RARS), a polypeptide of MSC complex. We also determined that the punctate GFP pro-EMAP II 1-70aa aggregate co-localizes and binds to the neurofilament light (NFL) subunit protein that is associated with pathologic neurofilament network disorganization and degeneration of motor neurons. These findings indicate the structure and binding interaction of Pro-EMAP II protein and suggest a role of this protein in the pathological neurodegenerative diseases.
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    Toward the Establishment of an In-Vitro Model of Glaucoma Using Human Induced Pluripotent Stem Cells
    (Office of the Vice Chancellor for Research, 2013-04-05) Gupta, Manav; Meyer, Jason S.
    Glaucoma is a severe neurodegenerative disease of the retina, leading to eventual irreversible blindness. A crucial element in the pathophysiology of all forms of glaucoma is the death of retinal ganglion cells (RGCs), a population of CNS neurons with their soma in the inner retina and axons fasciculating together to form the optic nerve. Retinal astrocytes have also been associated with glaucomatous neurodegeneration, although the direct or indirect role for these cells in the disease process remains unclear. Human induced pluripotent stem cells (iPSCs) provide a promising approach to develop cellular models to study such neurodegenerative diseases in vitro. Directed differentiation of several somatic cell types from human iPSCs have been successfully achieved with great implications for disease modeling and cell replacement strategies. Using existing lines of iPSCs, efforts were undertaken to successfully differentiate and characterize RGCs and astrocytes, the affected cell types in glaucoma. Using a previously described protocol, these cells were directed to differentiate toward a retinal fate through a step-wise process that proceeds through all of the major stages of neuroretinal development. The differentiation of RGCs was observed within the first forty days of differentiation whereas astrocytes were observed only after at least 70 days of differentiation. Using techniques including immunocytochemistry and RT-PCR, the individually derived somatic cells types were characterized by the expression of developmentally associated transcription factors specific to each cell type. Further approaches were undertaken to characterize the morphological differences between RGCs and other neuroretinal cell types derived in the process. Overall, this study demonstrates a robust method to derive the complex cell types associated with glaucoma, with prospects for further investigations into the developmental progression of the disease.