Elevation of the terminal complement activation products C5a and C5b-9 in ALS patient blood

  title={Elevation of the terminal complement activation products C5a and C5b-9 in ALS patient blood},
  author={Stefania Mantovani and Richard Gordon and J. K. Macmaw and Casey M. M. Pfluger and Robert D. Henderson and Peter G. Noakes and P A Mccombe and Trent M. Woodruff},
  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.

The Peripheral Immune System and Amyotrophic Lateral Sclerosis

There is strong preclinical evidence of benefit from immune modulation and further trials are currently underway, and their potential as future therapeutic targets for clinical intervention are reviewed.

Evaluation of Peripheral Immune Activation in Amyotrophic Lateral Sclerosis

The data supplement existing literature on understanding the role of peripheral immunity in ALS and found that the IgG levels were lower in early-onset ALS patients than in late-onsets ALS patients and HCs, and the correlations between age at onset of ALS and IgG or IgA levels were significant positive.

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.

Therapeutic Inhibition of the Complement System in Diseases of the Central Nervous System

The evidence implicating complement in diverse CNS disorders, from acute, such as traumatic brain or spine injury, to chronic, including demyelinating, neuroinflammatory, and neurodegenerative diseases is reviewed.

Complement Profiles in Patients with Amyotrophic Lateral Sclerosis: A Prospective Observational Cohort Study

ALS patients exhibit aberrant expression of selected mediators of the lectin complement pathway as well as increased activation of the terminal complement pathway, corroborating the notion that the complement system might be involved in the pathophysiology of ALS.

Aberrant Complement System Activation in Neurological Disorders

The aim of this review is to provide a summary of the literature on the emerging role of the complement system in certain brain disorders to provide new insight into potential therapeutic targets to ameliorate or slow progression of currently intractable disorders in the nervous system.



Role for terminal complement activation in amyotrophic lateral sclerosis disease progression

There is now a well-described fourth pathway of complement activation, termed the “extrinsic pathway,” which can bypass the traditional upstream activation pathways that are reliant on complement factor C3.

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.

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.

Role of complement in motor neuron disease: animal models and therapeutic potential of complement inhibitors.

Clinical and experimental findings suggest that targeting complement using specific inhibitors may represent a novel therapeutic approach to treating MND, and preliminary data indicates a specific pathogenic role for the activation fragment of complement C5 (C5a) in this disease.

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.

The complement factor C5a receptor is upregulated in NFL−/− mouse motor neurons

Reactions of the Immune System in Chronic Degenerative Neurological Diseases

ABSTRACT: Elements consistent with a cell mediated immune response were identified immunohistochemically in amyotrophic lateral sclerosis (ALS) spinal cord and Alzheimer disease (AD) hippocampus. T

Modulating inflammatory monocytes with a unique microRNA gene signature ameliorates murine ALS.

The results suggest that recruitment of inflammatory monocytes plays an important role in disease progression and that modulation of these cells is a potential therapeutic approach.