Complement upregulation and activation on motor neurons and neuromuscular junction in the SOD1 G93A mouse model of familial amyotrophic lateral sclerosis

  title={Complement upregulation and activation on motor neurons and neuromuscular junction in the SOD1 G93A mouse model of familial amyotrophic lateral sclerosis},
  author={Bianca Heurich and Nawal Bahia el Idrissi and Rossen M. Donev and Susanne Petri and Peter Claus and James W. Neal and Bryan Paul Morgan and Valeria Ramaglia},
  journal={Journal of Neuroimmunology},

Complement activation at the motor end-plates in amyotrophic lateral sclerosis

Evidence is provided that complement activation products are deposited on innervated motor end-plates in the intercostal muscle of ALS donors, indicating that complementactivation may precede end-plate denervation in human ALS.

Role of complement in ALS: regulating peripheral immune cells in skeletal muscle of hSOD1G93A mouse model of ALS

Results indicate that C5-C5aR1 and C3a-C3aR signalling regulates the migration of immune cells into the skeletal muscle during ALS disease progression, and the extent of immune cell influx is related to physiological ii function of skeletal muscle.

Gene expression profiling and functional studies of astrocytes in SOD1-related amyotrophic lateral sclerosis

The breadth of behaviours displayed by astrocytes during ALS disease progression is shown and will provide an important guide for future therapeutic intervention.

C1q induction and global complement pathway activation do not contribute to ALS toxicity in mutant SOD1 mice

Deletion of the C1q gene in mice expressing an ALS-causing mutant in SOD1 is demonstrated to produce changes in microglial morphology accompanied by enhanced loss, not retention, of synaptic densities during disease.

Complement components are upregulated and correlate with disease progression in the TDP-43Q331K mouse model of amyotrophic lateral sclerosis

Results indicate that similar to SOD1 transgenic animals, local complement activation and increased expression of C5aR1 may contribute to motor neuron death and neuromuscular junction denervation in the TDP-43Q331K mouse ALS model, which further validates C5 aR1 as a potential therapeutic target for ALS.

Dysregulation of the complement cascade in the hSOD1G93A transgenic mouse model of amyotrophic lateral sclerosis

Results indicate that local complement activation and increased expression of CD88 may contribute to motor neuron death and ALS pathology in the hSOD1G93A mouse, suggesting reducing complement-induced inflammation could be an important therapeutic strategy to treat ALS.

Role of Neuroinflammation in Amyotrophic Lateral Sclerosis: Cellular Mechanisms and Therapeutic Implications

The pharmacological therapies for ALS that target neuroinflammation, as well as recent advances in the field of stem cell therapy aimed at modulating the inflammatory environment to preserve the remaining MNs in ALS patients and animal models of the disease are summarized.

Transcriptomic indices of fast and slow disease progression in two mouse models of amyotrophic lateral sclerosis.

A set of key gene and molecular pathway indices of fast or slow disease progression which may prove useful in identifying potential disease modifiers responsible for the heterogeneity of human amyotrophic lateral sclerosis and which may represent valid therapeutic targets for ameliorating the disease course in humans are highlighted.

Temporospatial Analysis and New Players in the Immunology of Amyotrophic Lateral Sclerosis

The earliest reported immune responses with an emphasis on newly identified immune players in mutant superoxide dismutase 1 (mSOD1) transgenic mice, the gold standard mouse model for ALS, are discussed.



The Complement Factor C5a Contributes to Pathology in a Rat Model of Amyotrophic Lateral Sclerosis1

This study provides the first demonstration of an involvement of C5a in an ALS model and suggests that inhibitors of complement activation could be beneficial in the treatment of this neurodegenerative disease.

Amyotrophic lateral sclerosis is a distal axonopathy: evidence in mice and man

Restricted Expression of G86R Cu/Zn Superoxide Dismutase in Astrocytes Results in Astrocytosis But Does Not Cause Motoneuron Degeneration

Results indicate that 21q linked FALS is not a primary disorder of astrocytes, and that expression of mutant SOD1 restricted to astroCytes is not sufficient to cause motoneuron degeneration in vivo.

Toxicity from different SOD1 mutants dysregulates the complement system and the neuronal regenerative response in ALS motor neurons

Global, age-dependent changes in gene expression from rodent models of inherited ALS caused by dominant mutations in superoxide-dismutase 1 (SOD1) identified by using gene arrays and RNAs isolated from purified embryonic and adult motor neurons identified a set of targets for therapies for inherited ALS.

Microarray Analysis of the Cellular Pathways Involved in the Adaptation to and Progression of Motor Neuron Injury in the SOD1 G93A Mouse Model of Familial ALS

The changes described in the motor neuron transcriptome evolving during the disease course highlight potential novel targets for neuroprotective therapeutic intervention.

Neuron-Specific Expression of Mutant Superoxide Dismutase 1 in Transgenic Mice Does Not Lead to Motor Impairment

The animal model suggests that neuron-specific expression of ALS-associated mutant human SOD1 may not be sufficient for the development of the disease in mice, and suggests that the neurofilament light chain promoter may be responsible.

Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis

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.

Complement C3c and related protein biomarkers in amyotrophic lateral sclerosis and Parkinson's disease.

Transgenic-mouse model of amyotrophic lateral sclerosis.

  • M. Gurney
  • Biology, Medicine
    The New England journal of medicine
  • 1994
The experiments built on the studies of Dr. Brown and other members of a multicenter group that identified mutations of copper-zinc superoxide dismutase in some patients with a dominantly inherited form of amyotrophic lateral sclerosis.