PROTEOLYSIS IN THE MYELOPATHY OF ACQUIRED-IMMUNODEFICIENCY-SYNDROME -PREFERENTIAL LOSS OF THE C-8 COMPONENT OF MYELIN BASIC-PROTEIN

\Many patients with AIDS have a myelopathy characterized by vacuclizat ion of spinal cord white matter. The biochemical and molecular changes underlying this myelin disturbance have not yet been characterized. M yelin basic protein (MBP) is potentially important because it is a key structural protein of myelin with roles in compaction and stabilizati on. In the present study, we describe the steady-state protein concent ration of MBP in 46 patients with AIDS and 12 control subjects at auto psy. Patients with myelopathy exhibited no change in the abundance of the predominant 18.5- and 17.2-kd isoforms, but a 14-kd MBP-immunoreac tive degradation fragment was increased significantly. MBP degradation correlated significantly with the severity of histopathologic changes , including neutral lipid deposition, the density of vacuolated fibers , and the number of ferritin-stained activated microglia. Alkaline gel electrophoresis of isolated MBP showed preferential loss of the least cationic isomer (C-8). The concentration of MBP RNA in slot blots was normal in cords exhibiting myelopathy, and the ratio of mRNA correspo nding to the 18.5- and 17.2-kd MBP isoforms, measured using reverse tr anscriptase-PCR, was not altered. This study suggests that mononuclear phagocyte-mediated degradation of MBP may play a role in AIDS myelopa thy, and the preferential loss of the C-8 component of MBP may have me chanistic implications.