TDP-43 identified from a genome wide RNAi screen for SOD1 regulators.

PloS One
Balajee R SomalingaPhilip J Thomas

Abstract

Amyotrophic Lateral Sclerosis (ALS) is a late-onset, progressive neurodegenerative disease affecting motor neurons in the brain stem and spinal cord leading to loss of voluntary muscular function and ultimately, death due to respiratory failure. A subset of ALS cases are familial and associated with mutations in superoxide dismutase 1 (SOD1) that destabilize the protein and predispose it to aggregation. In spite of the fact that sporadic and familial forms of ALS share many common patho-physiological features, the mechanistic relationship between SOD1-associated and sporadic forms of the disease if any, is not well understood. To better understand any molecular connections, a cell-based protein folding assay was employed to screen a whole genome RNAi library for genes that regulate levels of soluble SOD1. Statistically significant hits that modulate SOD1 levels, when analyzed by pathway analysis revealed a highly ranked network containing TAR DNA binging protein (TDP-43), a major component of aggregates characteristic of sporadic ALS. Biochemical experiments confirmed the action of TDP-43 on SOD1. These results highlight an unexpected relationship between TDP-43 and SOD1 which may have implications in disease pathogenesis.

References

May 1, 1976·Annals of Clinical Biochemistry·J M Gutteridge
Oct 29, 1993·Science·J T Coyle, P Puttfarcken
Nov 1, 1995·Trends in Biochemical Sciences·P J ThomasP L Pedersen
Aug 26, 1998·Biochimica Et Biophysica Acta·M F Beal
Aug 26, 1998·Biochimica Et Biophysica Acta·A H Schapira
Jun 6, 2000·Journal of Biomolecular Screening·J H ZhangK R Oldenburg
Jun 27, 2000·Brain : a Journal of Neurology·M F Beal
Jun 2, 2001·The New England Journal of Medicine·L P Rowland, N A Shneider
Apr 23, 2002·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Gerry ShawFrank L Graham
Dec 17, 2002·Proceedings of the National Academy of Sciences of the United States of America·Mikael J LindbergMikael Oliveberg
May 6, 2003·Science·Majid HafezparastElizabeth M C Fisher
Dec 20, 2003·Nature·Dennis J Selkoe
Apr 11, 2006·Nuclear Receptor Signaling·Angie L Bookout, David J Mangelsdorf
Aug 25, 2006·Journal of Biomolecular Screening·Wendy J BroomRobert H Brown
Apr 13, 2007·Nature·Angelique W WhitehurstMichael A White
Jun 5, 2007·Neuroscience Letters·Janice RobertsonMichael J Strong
Jan 25, 2008·Journal of Biomolecular Screening·Namjin ChungBerta Strulovici
Feb 29, 2008·Proceedings of the National Academy of Sciences of the United States of America·Youhna M AyalaFrancisco E Baralle
Mar 1, 2008·Science·Jemeen SreedharanChristopher E Shaw
Jul 9, 2008·Amyotrophic Lateral Sclerosis : Official Publication of the World Federation of Neurology Research Group on Motor Neuron Diseases·Wendy J BroomRobert H Brown
Aug 16, 2008·The Journal of Biological Chemistry·Jayarama Krishnan BoseC-K James Shen
May 12, 2009·Nucleic Acids Research·Andrea D'AmbrogioFrancisco E Baralle
Aug 1, 2009·Nature Methods·Amanda BirminghamCaroline E Shamu
Jan 15, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Sami J BarmadaSteven Finkbeiner
Mar 6, 2010·Neuropathology and Applied Neurobiology·T F GendronL Petrucelli
Apr 20, 2010·Human Molecular Genetics·Clotilde Lagier-TourenneDon W Cleveland
Jan 22, 2011·The Journal of Biological Chemistry·Avin S LalmansinghPrabhakara P Reddi
Jan 25, 2011·Human Molecular Genetics·Karli K McDonaldChristine Vande Velde

❮ Previous
Next ❯

Citations

Jun 11, 2014·Experimental Neurology·Janis Bennion Callister, Stuart M Pickering-Brown
Dec 23, 2015·Trends in Molecular Medicine·Diana Caballero-HernandezDavid Pozo
Jun 10, 2021·Nature Reviews. Neuroscience·Débora LanznasterHélène Blasco
Mar 8, 2018·Journal of Proteome Research·Kathryn VolkeningMichael J Strong

❮ Previous
Next ❯

Methods Mentioned

BETA
transfection
PCR
Assay

Software Mentioned

Ingenuity
Image Quant
Ingenuity pathway analysis ( IPA )
IPA Core
IPA
Ensembl

Related Concepts

Related Feeds

Amyloid Lateral Sclerosis

Amyotrophic Lateral Sclerosis (ALS) is a progressive nervous system disease associated with the death of neurons that control voluntary muscles. Discover the latest research on ALS here.

ALS: Phenotypes

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disorder characterized phenotypically by progressive muscle weakness. Clinical phenotypes of ALS can be classified based on the pattern, level, and area of onset (e.g. bulbar, cervical, lumbar). Here is the latest research investigating phenotypes of ALS.

ALS: Genetics

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by muscle weakness. Here is the latest research investigating genetic alterations in this genetically heterogeneous disorder.

ALS: Genetics

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disorder characterized by muscle weakness. ALS is a genetically heterogeneous disorder with several causative genes. Here are the latest discoveries pertaining to the genetics of this disease.

ALS & FTD: TDP-43

TAR DNA-binding protein 43 (TDP-43) is a pathological protein identified in sporadic Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD). Here are the latest discoveries pertaining to TDP-43 and these diseases.

Birth Defects

Birth defects encompass structural and functional alterations that occur during embryonic or fetal development and are present since birth. The cause may be genetic, environmental or unknown and can result in physical and/or mental impairment. Here is the latest research on birth defects.