Neurons Susceptible to Neuronal Damage through a Novel Mechanism Mediated by Granzyme B

Summary
University of Alberta researchers report that neurons are susceptible to neuronal damage through a novel mechanism mediated by Granzyme B (GrB) and its receptor mannose-6-phosphate receptor (M6PR).Inhibiting this mechanism offers new approaches for future MS therapies. [Yohannes Haile, Katia Carmine Simmen, Dion Pasichnyk, Nicolas Touret, Thomas Simmen, Jian-Qiang Lu, R. Chris Bleackley, and Fabrizio Giuliani. Journal of Immunology, 2011, 187:4861-4872]

Details
Supported in part by the MS Society of Canada, University of Alberta researchers, Drs. Fabrizio Giuliani and Yohannes Haile and colleagues report promising findings from a study they conducted to further explore the mechanism responsible for axonal/neuronal degeneration in MS.  The team studied brain tissue from MS patients and found that neurons are susceptible to neuronal damage through a novel mechanism mediated by Granzyme B (GrB), a type of enzyme responsible for immune response. GrB can enter brain cells through a receptor known as mannose-6-phosphate receptor (M6PR), where it causes neuronal injury.

In MS, inflammatory cells invade the central nervous system (CNS) causing demyelination, axonal loss and neuronal injury or death. Recent research suggests that the axonal and neuronal damage may be the causal factor in the progression of permanent disability in MS. Inhibiting the activity of GrB and its ability to enter neurons through the receptor M6PR offers new approaches for future MS therapies.

The MS Society of Canada will follow the progress of this study area and provide updates when they become available.