title: Therapeutic targeting of complement to modify disease course and improve outcomes in neurological conditions.
abstract: The recognition that complement proteins are abundantly present and can have pathological roles in neurological conditions offers broad scope for therapeutic intervention. Accordingly, an increasing number of experimental investigations have explored the potential of harnessing the unique activation pathways, proteases, receptors, complexes, and natural inhibitors of complement, to mitigate pathology in acute neurotrauma and chronic neurodegenerative diseases. Here, we review mechanisms of complement activation in the central nervous system (CNS), and explore the effects of complement inhibition in cerebral ischemic-reperfusion injury, traumatic brain injury, spinal cord injury, Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease and Huntington's disease. We consider the challenges and opportunities arising from these studies. As complement therapies approach clinical translation, we provide perspectives on how promising complement-targeted therapeutics could become part of novel and effective future treatment options to improve outcomes in the initiation and progression stages of these debilitating CNS disorders.
authors.affiliation: School of Biomedical Sciences, The University of Queensland, Brisbane 4072, Australia.
authors.forename: Faith H
authors.initials: FH
authors.lastname: Brennan
authors.affiliation: School of Biomedical Sciences, The University of Queensland, Brisbane 4072, Australia.
authors.forename: John D
authors.initials: JD
authors.lastname: Lee
authors.affiliation: School of Biomedical Sciences, The University of Queensland, Brisbane 4072, Australia; Queensland Brain Institute, The University of Queensland, Brisbane 4072, Australia; Trauma, Critical Care and Recovery, Brisbane Diamantina Health Partners, The University of Queensland, Brisbane 4072, Australia.
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Ruitenberg
authors.affiliation: School of Biomedical Sciences, The University of Queensland, Brisbane 4072, Australia. Electronic address: t.woodruff@uq.edu.au.
authors.forename: Trent M
authors.initials: TM
authors.lastname: Woodruff
mesh_terms: D001921:Brain / Q000473:pathology*; D002986:Clinical Trials as Topic; D003167:Complement Activation; D051056:Complement Inactivating Agents / Q000627:therapeutic use*; D003165:Complement System Proteins / Q000378:metabolism*; D018450:Disease Progression; D006801:Humans; D058990:Molecular Targeted Therapy; D019636:Neurodegenerative Diseases / Q000276:immunology / Q000628:therapy*; D000066829:Neuroprotection; D016896:Treatment Outcome; D014947:Wounds and Injuries / Q000276:immunology / Q000628:therapy*
chemical_list: D051056:Complement Inactivating Agents; D003165:Complement System Proteins
keywords: C5a; Complement; Neurodegeneration; Neurotrauma; Stroke; Therapeutics