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The Relationship Between TDP-43 and Charcot-Marie-Tooth Disease

Undergraduate #64
Discipline: Biological Sciences
Subcategory: Cell and Molecular Biology

Justin A. Sherard - Delaware State University
Co-Author(s): Lauren J. Perry and Michael A. Gitcho, Delaware State University, Dover, DE



Charcot-Marie-Tooth (CMT) disease is a neurodegenerative disorder that damages both motor and sensory nerves. Motor neuron degeneration results in muscle weakness and atrophy, and degeneration of sensory nerves results in a reduced ability to feel heat, cold, and pain. Mutations in heat-shock protein 27 (HSP27) have been shown to segregate with juvenile forms of CMT. The neuropathology of CMT shows aggregation of TDP-43 in peripheral neurons. The heterogeneous nuclear ribonucleoprotein TDP-43 is the major pathological protein in frontotemporal dementia and motor neuron disease. We are interested in investigating the role TDP-43 plays in the pathogenesis of Charcot-Marie-Tooth disease. Through immunoprecipitation and proteomics we have discovered a unique complex interaction between TDP-43, AUF1, and HSP27 that may indicate a functional role of TDP-43 in this devastating disease. We hypothesize that mutations in HSP27 will alter localization of endogenous TDP-43 in a motor neuron-like cell line (NSC34) similar to what is seen in Charcot-Marie-Tooth disease. We are in hopes that this work will give us a better understanding of the pathogenesis of Charcot-Marie-Tooth disease.

Funder Acknowledgement(s): Alzheimer’s Association New Investigator Research Grant NIRG-12-241456 ; NIH-NIA K01 1K01AG042500-01A1 ;NIH-NIGMS IDeA (P20 GM103446) INBRE Pilot Grant

Faculty Advisor: Michael Gitcho,

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This material is based upon work supported by the National Science Foundation (NSF) under Grant No. DUE-1930047. Any opinions, findings, interpretations, conclusions or recommendations expressed in this material are those of its authors and do not represent the views of the AAAS Board of Directors, the Council of AAAS, AAAS’ membership or the National Science Foundation.

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