Potential intervention by vaccinia virus complement control protein of the signals contributing to the progression of central nervous system injury to Alzheimer's disease.
Traumatic brain injury (TBI) is one of the few known risk factors for Alzheimers disease (AD) and for depression. The mechanisms by which trauma causes delayed cognitive deficits are largely unknown. In recent studies, it was demonstrated that the complement system (an important component of the immune system and a mediator of inflammation) is activated both in human AD and following experimental TBI in rats. Amyloid proteins are also present in AD and following TBI, and are known to activate complement in vitro. Based on these and other previous studies, it was hypothesized that regulation of the complement system will attenuate the long-term consequences of TBI. Vaccinia virus complement control protein (VCP) is a protein encoded by vaccinia virus. It blocks both the classic and alternative pathways of complement activation in vitro, and by doings so prevents the generation of proinflammatory chemotactic factors. Based on in vitro studies VCP can block the complement activation by the amyloid beta peptide. Using a fluid percussion rat model that causes traumatic brain injury (TBI), it was found that VCP significantly enhances functional recovery as determined by the Morris Water Maze test. Taken togther these studies indicate that potentially VCP could block molecular signals such as the formation of amyloid beta or the activation of complement to inhibit formation of AD following TBI.
Kotwal
Girish J
GJ
Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, Kentucky 40202, USA. gjk01@gwise.louisville.edu
Lahiri
Debomoy K
DK
Hicks
Ramona
R
D000544:Alzheimer Disease / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D006259:Craniocerebral Trauma / Q000503:physiopathology / Q000821:virology; D018450:Disease Progression; D006801:Humans; D007858:Learning; D008568:Memory; D051381:Rats; D015398:Signal Transduction / Q000502:physiology*; D014764:Viral Proteins / Q000502:physiology*
D014764:Viral Proteins; C066459:complement-control protein, Vaccinia virus