Journal ArticleDOI
Wild-type nonneuronal cells extend survival of SOD1 mutant motor neurons in ALS mice.
A. M. Clement,Minh Dang Nguyen,E. A. Roberts,E. A. Roberts,M. L. Garcia,M. L. Garcia,Séverine Boillée,Séverine Boillée,M. Rule,Andrew P. McMahon,Wilder Doucette,D. Siwek,Robert J. Ferrante,Robert H. Brown,Jean-Pierre Julien,Lawrence S.B. Goldstein,Lawrence S.B. Goldstein,Don W. Cleveland,Don W. Cleveland +18 more
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Nonneuronal cells that do not express mutant SOD1 delay degeneration and significantly extend survival of mutant-expressing motor neurons.Abstract:
The most common inherited [correct] form of amyotrophic lateral sclerosis (ALS), a neurodegenerative disease affecting adult motor neurons, is caused by dominant mutations in the ubiquitously expressed Cu-Zn superoxide dismutase (SOD1) In chimeric mice that are mixtures of normal and SOD1 mutant-expressing cells, toxicity to motor neurons is shown to require damage from mutant SOD1 acting within nonneuronal cells Normal motor neurons in SOD1 mutant chimeras develop aspects of ALS pathology Most important, nonneuronal cells that do not express mutant SOD1 delay degeneration and significantly extend survival of mutant-expressing motor neuronsread more
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Mechanisms underlying inflammation in neurodegeneration.
TL;DR: There is evidence for a remarkable convergence in the mechanisms responsible for the sensing, transduction, and amplification of inflammatory processes that result in the production of neurotoxic mediators in neurodegenerative diseases.
Journal ArticleDOI
Astrocytes, from brain glue to communication elements: the revolution continues.
Andrea Volterra,Jacopo Meldolesi +1 more
TL;DR: The recent recognition that astrocytes are organized in separate territories and possess active properties — notably a competence for the regulated release of 'gliotransmitters', including glutamate — has enabled us to develop an understanding of previously unknown functions for astroCytes.
Journal ArticleDOI
Microglial physiology: unique stimuli, specialized responses
TL;DR: A wealth of data now demonstrate that the microglia have very diverse effector functions, in line with macrophage populations in other organs, and the term activatedmicroglia needs to be qualified to reflect the distinct and very different states of activation-associated effector function in different disease states.
Journal ArticleDOI
Onset and Progression in Inherited ALS Determined by Motor Neurons and Microglia
Séverine Boillée,Koji Yamanaka,Christian S. Lobsiger,Neal G. Copeland,Nancy A. Jenkins,George Kassiotis,George Kollias,Don W. Cleveland +7 more
TL;DR: Onset and progression of amyotrophic lateral sclerosis represent distinct disease phases defined by mutant action within different cell types to generate non–cell-autonomous killing of motor neurons; these findings validate therapies, including cell replacement, targeted to the non-neuronal cells.
Journal ArticleDOI
Reactive astrocytes protect tissue and preserve function after spinal cord injury.
Jill R. Faulkner,Julia E. Herrmann,Michael J. Woo,Keith E. Tansey,Ngan B. Doan,Michael V. Sofroniew +5 more
TL;DR: The findings show that reactive astrocytes provide essential activities that protect tissue and preserve function after mild or moderate SCI, and suggest that identifying ways to preserve reactive astracytes, to augment their protective functions, or both, may lead to novel approaches to reducing secondary tissue degeneration and improving functional outcome after SCI.
References
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Journal ArticleDOI
Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis
TL;DR: Tight genetic linkage between FALS and a gene that encodes a cytosolic, Cu/Zn-binding superoxide dismutase (SOD1), a homodimeric metalloenzyme that catalyzes the dismutation of the toxic superoxide anion O–2 to O2 and H2O2 is reported.
Journal ArticleDOI
Motor neuron degeneration in mice that express a human Cu,Zn superoxide dismutase mutation.
Mark E. Gurney,Haifeng Pu,Arlene Y. Chiu,Mauro C. Dal Canto,Cynthia Y. Polchow,Denise D. Alexander,Jan Caliendo,Afif Hentati,Young W. Kwon,Han Xiang Deng,W. Chen,Ping Zhai,Robert L. Sufit,Teepu Siddique +13 more
TL;DR: In this article, the authors found that mutations of human Cu,Zn superoxide dismutase (SOD) contribute to the pathogenesis of familial amyotrophic lateral sclerosis (ALS).
Journal ArticleDOI
An adverse property of a familial ALS-linked SOD1 mutation causes motor neuron disease characterized by vacuolar degeneration of mitochondria
Philip C. Wong,Carlos A. Pardo,David R. Borchelt,Michael K. Lee,Neal G. Copeland,Nancy A. Jenkins,Sangram S. Sisodia,Don W. Cleveland,Don W. Cleveland,Donald L. Price +9 more
TL;DR: Mutations in Cu/Zn superoxide dismutase cause a subset of cases of familial amyotrophic lateral sclerosis, and four lines of mice accumulating one of these mutant proteins (G37R) develop severe, progressive motor neuron disease.
Journal ArticleDOI
From charcot to lou gehrig: deciphering selective motor neuron death in als
TL;DR: Insights into abnormalities in two genes, together with errors in the handling of synaptic glutamate and the potential excitotoxic response that this alteration provokes, have provided leads for the development of new strategies to identify an as yet elusive remedy for this progressive, fatal disorder.
Journal ArticleDOI
ALS-Linked SOD1 Mutant G85R Mediates Damage to Astrocytes and Promotes Rapidly Progressive Disease with SOD1-Containing Inclusions
Lucie Bruijn,Mark W. Becher,Michael K. Lee,K. L. Anderson,Nancy A. Jenkins,Neal G. Copeland,Sangram S. Sisodia,Jeffrey D. Rothstein,David R. Borchelt,Donald L. Price,Don W. Cleveland +10 more
TL;DR: It is reported here that even low levels of another mutant, G85R, cause motor neuron disease characterized by an extremely rapid clinical progression, without changes in SOD1 activity.