Mutant dynein (Loa) triggers proprioceptive axon loss that extends survival only in the SOD1 ALS model with highest motor neuron death.

Proceedings of the National Academy of Sciences of the United States of America
Hristelina S IlievaDon W Cleveland

Abstract

Dominant mutations in cytoplasmic dynein (Loa or Cra) have been reported to provoke selective, age-dependent killing of motor neurons, while paradoxically slowing degeneration and death of motor neurons in one mouse model of an inherited form of ALS. Examination of Loa animals reveals no degeneration of large caliber alpha-motor neurons beyond an age-dependent loss (initiating only after 18 months) that was comparable in Loa and wild-type littermates. Absence of Loa-mediated alpha-motor neuron loss contrasted with dramatic, sustained, mutant dynein-mediated postnatal loss of lumbar proprioceptive sensory axons, accompanied by decreased excitatory glutamatergic inputs to motor neurons. In mouse models of inherited ALS caused by mutations in superoxide dismutase (SOD1), mutant dynein modestly prolonged survival in the one mouse model with the most extensive motor neuron loss (SOD(G93A)) while showing marginal (SOD(G85R)) or no (SOD(G37R)) benefit in models with higher numbers of surviving motor neurons at end stage. These findings support a noncell autonomous, excitotoxic contribution from proprioceptive sensory neurons that modestly accelerates disease onset in inherited ALS.

References

Oct 1, 1987·Journal of the Neurological Sciences·M DibJ Bezian
Jul 1, 1995·Annals of Neurology·J D RothsteinR W Kuncl
Dec 23, 1998·Proceedings of the National Academy of Sciences of the United States of America·P PasinelliR H Brown
Jan 31, 2002·Proceedings of the National Academy of Sciences of the United States of America·David S HowlandJeffrey D Rothstein
May 6, 2003·Science·Majid HafezparastElizabeth M C Fisher
Sep 18, 2003·Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders : Official Publication of the World Federation of Neurology, Research Group on Motor Neuron Diseases·Azlina Ahmad-AnnuarElizabeth M C Fisher
May 25, 2005·The Journal of Cell Biology·Dairin KieranLinda Greensmith
Jul 9, 2005·Proceedings of the National Academy of Sciences of the United States of America·Christian S LobsigerDon W Cleveland
Jul 23, 2005·Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders : Official Publication of the World Federation of Neurology, Research Group on Motor Neuron Diseases·Francesca AchilliElizabeth M C Fisher
Jan 24, 2006·Experimental Neurology·M TeuchertA C Ludolph
Mar 21, 2006·Amyotrophic Lateral Sclerosis : Official Publication of the World Federation of Neurology Research Group on Motor Neuron Diseases·Paresh R ShahElizabeth M C Fisher
Jun 3, 2006·Science·Séverine BoilléeDon W Cleveland
Oct 18, 2006·Proceedings of the National Academy of Sciences of the United States of America·David R BeersStanley H Appel
Dec 28, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Xiang-Jun ChenBrian Popko
Feb 5, 2008·Nature Neuroscience·Koji YamanakaDon W Cleveland

❮ Previous
Next ❯

Citations

Nov 26, 2010·Nature Cell Biology·Kassandra M Ori-McKenneyRichard B Vallee
Nov 10, 2010·Proceedings of the National Academy of Sciences of the United States of America·Lynsey G BilslandGiampietro Schiavo
Aug 17, 2011·Proceedings of the National Academy of Sciences of the United States of America·Veena Prahlad, Richard I Morimoto
Feb 6, 2013·Proceedings of the National Academy of Sciences of the United States of America·Eveline S ArnoldDon W Cleveland
Apr 7, 2009·Antioxidants & Redox Signaling·Jordi Magrané, Giovanni Manfredi
Oct 13, 2011·Integrative and Comparative Biology·Katharina A Quinlan
Jan 29, 2011·Journal of Biomedicine & Biotechnology·L Van Den Bosch
May 27, 2011·Neural Development·Kassandra M Ori-McKenney, Richard B Vallee
Nov 22, 2012·Neural Development·Melissa M Langworthy, Bruce Appel
Feb 25, 2011·PloS One·Stephanie L CourchesneRosalind A Segal
Apr 8, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Gareth T BanksElizabeth M C Fisher
Jan 21, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·M A LimR G Kalb
Apr 24, 2014·Brain : a Journal of Neurology·Caroline A GarrettMajid Hafezparast
Jan 7, 2014·Antioxidants & Redox Signaling·Marija Sajic
Oct 1, 2013·Neurochemical Research·Magdalena Kuźma-KozakiewiczAnna Barańczyk-Kuźma
Dec 3, 2009·The Journal of Cell Biology·Hristelina IlievaDon W Cleveland
Mar 23, 2011·Pharmacology & Therapeutics·Judith Eschbach, Luc Dupuis
May 4, 2010·Trends in Neurosciences·Eran PerlsonErika L F Holzbaur
May 8, 2009·Revue neurologique·P-F PradatUNKNOWN coordination des centres de prise en charge des patients atteints de SLA
Aug 13, 2015·Biochimica Et Biophysica Acta·Jae Keun LeeEui-Ju Choi
Jun 24, 2015·Journal of Neurology·Alleene V StricklandMichaela Auer-Grumbach
Jul 21, 2012·Neurobiology of Disease·Khanh T NguyenGavriel David
Jun 12, 2013·Translational Neuroscience·Xin-An LiuSathyanarayanan V Puthanveettil
Mar 26, 2013·Biochimica Et Biophysica Acta·Philip McGoldrickLinda Greensmith
Sep 17, 2013·Trends in Neurosciences·Giampietro SchiavoElizabeth M C Fisher

❮ 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.

© 2022 Meta ULC. All rights reserved