2017
DOI: 10.1186/s13395-017-0128-8
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Abstract: BackgroundThe terminal pathway of the innate immune complement system is implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). Terminal complement activation leads to generation of C5a, which through its receptor, C5aR1, drives immune cell recruitment and activation. Importantly, genetic or pharmacological blockage of C5aR1 improves motor performance and reduces disease pathology in hSOD1G93A rodent models of ALS. In this study, we aimed to explore the potential mechanisms of C5aR1-mediated pa… Show more

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Cited by 47 publications
(56 citation statements)
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“…Lobsiger et al showed that genetic deletion of C1q and C3 from ALS mice did not affect the overall onset and progression of the disease, thus suggesting that C1q induction and classical or alternative complement pathway activation do not contribute significantly to mSOD1-mediated ALS pathogenesis in mice ( 112 ). On the contrary, others have reported that terminal complement activation and C5a production occurred in skeletal muscle tissue of SOD1 G93A mice ( 113 ). Local activation and increased expression of C5a–C5aR1 signaling contributed to the recruitment of macrophages that might have accelerated muscle denervation and MN death in SOD1 G93A mice ( 113 , 114 ).…”
Section: Neuroinflammation In Als: Perspective On Cellular Basismentioning
confidence: 92%
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“…Lobsiger et al showed that genetic deletion of C1q and C3 from ALS mice did not affect the overall onset and progression of the disease, thus suggesting that C1q induction and classical or alternative complement pathway activation do not contribute significantly to mSOD1-mediated ALS pathogenesis in mice ( 112 ). On the contrary, others have reported that terminal complement activation and C5a production occurred in skeletal muscle tissue of SOD1 G93A mice ( 113 ). Local activation and increased expression of C5a–C5aR1 signaling contributed to the recruitment of macrophages that might have accelerated muscle denervation and MN death in SOD1 G93A mice ( 113 , 114 ).…”
Section: Neuroinflammation In Als: Perspective On Cellular Basismentioning
confidence: 92%
“…On the contrary, others have reported that terminal complement activation and C5a production occurred in skeletal muscle tissue of SOD1 G93A mice ( 113 ). Local activation and increased expression of C5a–C5aR1 signaling contributed to the recruitment of macrophages that might have accelerated muscle denervation and MN death in SOD1 G93A mice ( 113 , 114 ). Selective inhibition of C5a–C5aR1 signaling ameliorated disease pathology, reduced motor symptoms, and extended the survival of SOD1 G93A mice ( 110 , 115 ).…”
Section: Neuroinflammation In Als: Perspective On Cellular Basismentioning
confidence: 92%
“…Animal studies also indicate a role for terminal complement activation in motor neuron degeneration. In SOD1 and TDP43 animal models of ALS there is evidence of complement activation (119,120), and genetic deficiency or pharmacological inhibition of the C5a receptor, C5aR1, is protective in rodent SOD1 G93A models (73,(121)(122)(123). A comprehensive review of the involvement of complement in ALS has recently been written (124).…”
Section: Complement Systemmentioning
confidence: 99%
“…Briefly, in ALS, elevated concentrations of complement activation products such as C1q, C3b, C5a, and MAC (C5b‐9) are detected in serum, cerebrospinal fluid, spinal cord and motor cortex of ALS patients 3 . Moreover, in rodent models of ALS such as SOD1 G93A mice, increased expression of these activation products are also observed in the lumbar spinal cord and tibialis anterior muscles throughout disease progression 10‐12 . In addition, studies in multiple ALS mouse models, and human postmortem tissue have identified an increase in terminal C5aR1 expression localized to motor neurons and activated microglia in the spinal cord and macrophages in the tibialis anterior skeletal muscles 11‐13 .…”
Section: The Complement System and Alsmentioning
confidence: 99%