Complement for AD


Presentation Description

As an important factor in the pathogenesis of numerous diseases of the CNS, the complement system has been developed to the potential biomarkers and new drugs targets.


Presentation Transcript

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Neurology Neurology As an essential part of the immune system the complement system has traditionally been considered as a first defense line of innate immunity against invading pathogenesis. However over the past few decades several additional roles have been uncovered including the elimination of immune complex removal of apoptotic cells and debris modulation of metabolic and regenerative processes and regulation of adaptive immunity. Complement is activated through one or more of three pathways: the classical lectin or alternative pathway and it is regulated tightly by several mechanisms to prevent host injury. In the central nervous system CNS complement proteins can be induced in all cell types and play similar roles in host defense. There are several lines of evidence indicating that the pathogenesis of CNS diseases is closely related to over-activation and/or under-regulation of complement. There are several physiological roles of complement in the CNS: Sensor and Orchestrator of the Innate Immune Response Microglia and astrocyte are acknowledged primary immune cells of the CNS which can utilize the components of complement system to provide the brain with immune sensors and response capabilities. C1q the initiating protein of the classical complement cascade has been observed to bind

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to apoptotic cells including neurons and then mediates damaged or dying neurons to be cleared by microglia thus prevents the release of toxic components to avoid additional insult or injury. In addition to its historic role in recognizing foreign materials and initiating of complement activation C1q has also been shown to be produced in neurons to play a direct protective role by enhancing the clearance of apoptotic cells. Inflammation and neurodegeneration in Alzheimer’s disease AD are partially mediated by complement activation. Beyond Immune Surveillance The microglia in CNS can response to C5a stimulation thus upregulate the glutamate transporter GLT-1 and increase glutamate uptake which may provide protection against glutamate-mediated excitotoxicity. C5a has also been observed to provide direct protection to differentiated SH-SY5Y neuroblastoma cells against β-amyloid. Complement components have also been evaluated to take part in multiple physiological processes including the developmental refinement of synapses within the visual system. Neuropathogenic Mediator in Numerous CNS Disease States C5a has the potential neuroprotective activities which can activate CD88 to play a deleterious role in CNS disease. Besides AD several neurodegenerative diseases such as Huntington’s disease HD and amyotrophic lateral sclerosis ALS all seem to indicate C5a induced CD88 activation as a driver of CNS pathology.

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Fig.1 Propagation of disease pathology by complement in CNS disease. Woodruff et al. 2010 As an important factor in the pathogenesis of numerous diseases of the CNS including infection autoimmune and degenerative disorders neuropsychiatric disease the complement system has been developed to the potential biomarkers and new drugs targets.

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