Academic Commons

Theses Doctoral

The ALS Genes TDP-43 and FUS/TLS Regulate a Common Pathway in the Nervous System of Drosophila Melanogaster

Brent, Jonathan Robert

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disorder characterized by the dysfunction and death of motor neurons. Patients afflicted with this condition commonly experiences muscle weakness that progresses to generalized paralysis. Although most ALS cases are sporadic, mutations in several human genes of divergent molecular function have been linked to the development of ALS. Recently, two new ALS genes, TDP-43 and FUS, were identified that have structural similarities suggesting that they may function in a common process. TDP-43 and FUS have both been implicated in a number of cellular functions, including the regulation of splicing, transcription, and microRNA processing. The work in this thesis includes studies that identified roles for TDP-43 and FUS in the health and function of the nervous system of Drosophila melanogaster. Genetic and biochemical studies were used to define the molecular relationships between TDP-43 and FUS, placing TDP-43 upstream of FUS in a common pathway that is important for the function and health of the nervous system. The finding that TDP-43 and FUS interact suggests that they regulate a common disease pathway that is disrupted in ALS and that therapeutic intervention in this pathway may ameliorate many of the symptoms of the disease.

Files

  • thumnail for Brent_columbia_0054D_10862.pdf Brent_columbia_0054D_10862.pdf application/x-pdf 33.8 MB Download File

More About This Work

Academic Units
Cellular, Molecular, Structural, and Genetic Studies
Thesis Advisors
McCabe, Brian D.
Degree
Ph.D., Columbia University
Published Here
July 2, 2012
Academic Commons provides global access to research and scholarship produced at Columbia University, Barnard College, Teachers College, Union Theological Seminary and Jewish Theological Seminary. Academic Commons is managed by the Columbia University Libraries.