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Georgia Journal of Science

Article Title

BIOLOGICAL EFFECTS OF BENZOTHIAZOLE DERIVATIVES: ALS CELLS AND THE EFFECTS OF THE TDP-43 PROTEIN**

Abstract

ALS (amyotrophic lateral sclerosis) is a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord. Motor neurons run from the brain to the muscles by going through the spinal cord. When the motor neurons stop functioning, the ability of the brain to initiate and control muscle movement is lost. With voluntary muscle action progressively affected, patients may lose the ability to speak, eat, move, and breathe. Few drugs are known to treat against ALS. Presently, Riluzole is the only FDA-approved drug for ALS, and. this drug has been shown to have little to no effects on the treatment. Riluzole is derived from a class of compounds known as benzothiazoles. Benzothiazoles are heterocyclic compounds that contain a benzene ring and a sulfur and nitrogen within a cyclopentane group referred to as thiazoles. Benzothiazoles are ubiquitously found in clinical setting, specifically as fungicide to a cancer targeting agent. TDP-43 protein (TDP-43) is a transactive response DNA binding protein. TDP-43 is protein found in the nucleus of cells and it normally participates in several mechanisms of mRNA metabolism. Certain amino acids of the C-terminus in the protein can become phosphorylated and the protein folds onto itself in a conformation that renders it inactive with prion-like characteristics. Thus causing buildup of the proteins in the cell and delaying cytosolic degradation of the proteins which causes cellular damage and death. Benzothiazole-derivatives have been synthesized and will be tested on HEK-293T cells, wild-type TDP-43 protein, and HEK293T cells transfected with TDP43 protein in order to discern what substituents are the most effective on the treatment of ALS.

Acknowledgements

SRACE, LSAMP, Dept of Chemistry, Columbus State University, Dept of Biology, Columbus State University

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