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Full-Text Articles in Diseases

Emerging Cellular And Molecular Strategies For Enhancing Central Nervous System (Cns) Remyelination., Mohammad Abu-Rub, Robert H Miller Jun 2018

Emerging Cellular And Molecular Strategies For Enhancing Central Nervous System (Cns) Remyelination., Mohammad Abu-Rub, Robert H Miller

Anatomy and Regenerative Biology Faculty Publications

Myelination is critical for the normal functioning of the central nervous system (CNS) in vertebrates. Conditions in which the development of myelin is perturbed result in severely compromised individuals often with shorter lifespans, while loss of myelin in the adult results in a variety of functional deficits. Although some form of spontaneous remyelination often takes place, the repair process as a whole often fails. Several lines of evidence suggest it is feasible to develop strategies that enhance the capacity of the CNS to undergo remyelination and potentially reverse functional deficits. Such strategies include cellular therapies using either neural or mesenchymal …


Pharmaceutical Integrated Stress Response Enhancement Protects Oligodendrocytes And Provides A Potential Multiple Sclerosis Therapeutic., Sharon W Way, Joseph R Podojil, Benjamin L Clayton, Anita Zaremba, Tassie L Collins, Rejani B Kunjamma, Andrew P Robinson, Pedro Brugarolas, Robert H. Miller, Stephen D Miller, Brian Popko Mar 2015

Pharmaceutical Integrated Stress Response Enhancement Protects Oligodendrocytes And Provides A Potential Multiple Sclerosis Therapeutic., Sharon W Way, Joseph R Podojil, Benjamin L Clayton, Anita Zaremba, Tassie L Collins, Rejani B Kunjamma, Andrew P Robinson, Pedro Brugarolas, Robert H. Miller, Stephen D Miller, Brian Popko

Anatomy and Regenerative Biology Faculty Publications

Oligodendrocyte death contributes to the pathogenesis of the inflammatory demyelinating disease multiple sclerosis (MS). Nevertheless, current MS therapies are mainly immunomodulatory and have demonstrated limited ability to inhibit MS progression. Protection of oligodendrocytes is therefore a desirable strategy for alleviating disease. Here we demonstrate that enhancement of the integrated stress response using the FDA-approved drug guanabenz increases oligodendrocyte survival in culture and prevents hypomyelination in cerebellar explants in the presence of interferon-γ, a pro-inflammatory cytokine implicated in MS pathogenesis. In vivo, guanabenz treatment protects against oligodendrocyte loss caused by CNS-specific expression of interferon-γ. In a mouse model of MS, experimental …