title: Deficiency of the complement regulator CD59a exacerbates Wallerian degeneration.
abstract: The complement system is implicated in Wallerian degeneration (WD). We have previously shown that the membrane attack complex (MAC), the terminal activation product of the complement cascade, mediates rapid axonal degradation and myelin clearance during WD after peripheral nerve injury. In this study we analyzed the contribution of CD59a, a cell membrane negative regulator of the MAC, to WD. Following injury, the level of MAC deposition was higher in the CD59a deficient mice than wildtypes whereas the residual axonal content was lower in CD59a deficient mice than wildtypes, strongly implicating MAC as a determinant of axonal damage during WD. The number of endoneurial macrophages was significantly higher in CD59a deficient mice compared to wildtypes at 1 day post-injury. These findings are relevant to the understanding of the mechanisms of axon loss in injury and disease.
authors.affiliation: Neurogenetics Laboratory, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Valeria
authors.initials: V
authors.lastname: Ramaglia
authors.forename: Rosalind Helen Mary
authors.initials: RH
authors.lastname: King
authors.forename: Bryan Paul
authors.initials: BP
authors.lastname: Morgan
authors.forename: Frank
authors.initials: F
authors.lastname: Baas
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology; D018957:CD59 Antigens / Q000235:genetics* / Q000502:physiology; D011232:Chemical Precipitation; D003186:Complement C9 / Q000378:metabolism; D003165:Complement System Proteins / Q000378:metabolism; D018450:Disease Progression; D008264:Macrophages / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D013997:Time Factors; D020196:Trauma, Nervous System / Q000235:genetics / Q000473:pathology; D014855:Wallerian Degeneration / Q000235:genetics* / Q000473:pathology
chemical_list: D018957:CD59 Antigens; C539311:CD59a protein, mouse; D003186:Complement C9; D003165:Complement System Proteins