Interplay between TDP-43 and docosahexaenoic acid-related processes in amyotrophic lateral sclerosis

Neurobiology of Disease
Daniel CacabelosManuel Portero-Otin

Abstract

Docosahexaenoic acid (DHA), a key lipid in nervous system homeostasis, is depleted in the spinal cord of sporadic amyotrophic lateral sclerosis (sALS) patients. However, the basis for such loss was unknown. DHA synthetic machinery was evaluated in spinal cord samples from ALS patients and controls by immunohistochemistry and western blot. Further, lipid composition was measured in organotypic spinal cord cultures by gas chromatography and liquid chromatography coupled to mass spectrometry. In these samples, mitochondrial respiratory functions were measured by high resolution respirometry. Finally, Neuro2-A and stem cell-derived human neurons were used for evaluating mechanistic relationships between TDP-43 aggregation, oxidative stress and cellular changes in DHA-related proteins. ALS is associated to changes in the spinal cord distribution of DHA synthesis enzymatic machinery comparing ten ALS cases and eight controls. We found increased levels of desaturases (ca 95% increase, p<0.001), but decreased amounts of DHA-related β-oxidation enzymes in ALS samples (40% decrease, p<0.05). Further, drebrin, a DHA-dependent synaptic protein, is depleted in spinal cord samples from ALS patients (around 40% loss, p<0.05). In contrast, chr...Continue Reading

References

Jul 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·J D RothsteinR W Kuncl
Apr 29, 1998·Journal of the Neurological Sciences·F R WiedemannW S Kunz
Jun 7, 2002·The Journal of Biological Chemistry·Marina MattiazziGiovanni Manfredi
Jan 23, 2003·Prostaglandins, Leukotrienes, and Essential Fatty Acids·Xiao Qiu
Aug 13, 2003·The EMBO Journal·Karim S EchtayMartin D Brand
Sep 23, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Olivia HurtadoMaría A Moro
Mar 15, 2005·Reproduction, Nutrition, Development·Jean-Marc AlessandriMonique Lavialle
Aug 25, 2007·Brain : a Journal of Neurology·Ekaterina V IlievaManuel Portero-Otín
Dec 15, 2007·Annals of the New York Academy of Sciences·Reinald PamplonaManuel Portero-Otin
Apr 29, 2008·Journal of Lipid Research·Charlotte AnderssonSteven D Freedman
Sep 16, 2008·Analytica Chimica Acta·Roslyn DillonB Ganesh Bhat
Apr 29, 2010·The FEBS Journal·Emanuele BurattiFrancisco Baralle
Jul 10, 2010·Journal of Psychiatric Research·Yanhong Liu, Robert K McNamara
Jul 28, 2010·Proceedings of the National Academy of Sciences of the United States of America·Po-Min ChiangPhilip C Wong
Mar 2, 2011·Nature Reviews. Drug Discovery·Alan H Nagahara, Mark H Tuszynski
May 31, 2011·Biochemical and Biophysical Research Communications·Françoise Le BorgneJean Demarquoy
Jun 15, 2011·Journal of Neurochemistry·Kai-Hui SunKavita Shah
Jun 28, 2011·Acta Neuropathologica·Victòria AyalaManuel Portero-Otin
Nov 2, 2011·PloS One·Igor NepliouevJonathan A Stiber
Sep 13, 2012·Neuroreport·Masahiro NakamoriMasayasu Matsumoto
Aug 24, 2013·PloS One·Nancy R StallingsJeffrey L Elliott
Aug 28, 2013·The Journal of Cell Biology·Daniel C WorthPhillip R Gordon-Weeks
Jul 16, 2014·JAMA Neurology·Kathryn C FitzgeraldAlberto Ascherio
Sep 18, 2015·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Zhuo-Hao LiuAdina T Michael-Titus

❮ Previous
Next ❯

Citations

Feb 16, 2017·Journal of Neurochemistry·Tomoaki ShiraoYuko Sekino
Mar 4, 2018·Scientific Reports·M SzelechowskiR Rossignol
Jun 17, 2020·Expert Review of Neurotherapeutics·Roberta BonomoDebra J Skene
Jul 15, 2020·Epilepsia·Thaís Caroline Dallabona DombroskiAntonio Roberto Martins
Nov 13, 2019·Expert Opinion on Therapeutic Targets·Pei ShangJiachun Feng
Jul 29, 2017·Clinical and Translational Medicine·Rafael ZárateCovadonga Rodríguez
Nov 24, 2018·Journal of Molecular Neuroscience : MN·Surabhi BhatiaGlenda M Halliday
Nov 28, 2020·Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova·A V AlessenkoA A Ustyugov
Apr 28, 2021·Journal of Neurochemistry·Omar Ramírez-NuñezManuel Portero-Otin

❮ Previous
Next ❯

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.

Adult Stem Cells

Adult stem cells reside in unique niches that provide vital cues for their survival, self-renewal, and differentiation. They hold great promise for use in tissue repair and regeneration as a novel therapeutic strategies. Here is the latest research.

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.

ALS: Pathogenic Mechanisms

Amyotrophic Lateral Sclerosis is a progressive neurodegenerative disorder characterized by muscle weakness. Here is the latest research investigating pathogenic mechanisms that underlie this genetically heterogeneous disorder.

Related Papers

Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders : Official Publication of the World Federation of Neurology, Research Group on Motor Neuron Diseases
S AppelD R Mosier
© 2021 Meta ULC. All rights reserved