Giuseppe Scalabrino, MD
University of Milan, Italy
Title: Involvement of normal prions (PrPCs) in some human myelin diseases
Biography
Biography: Giuseppe Scalabrino, MD
Abstract
We have experimentally demonstrated that cobalamin (Cbl) deficiency increases normal cellular prion (PrPC) levels in rat spinal cord (SC) and cerebrospinal fluid (CSF), and decreases PrPC-mRNA levels in rat SC. Repeated intracerebroventricular administrations of anti-octapeptide repeat-PrPC-region antibodies to Cbl-deficient (Cbl-D) rats prevent SC myelin lesions, and the administrations of PrPCs to otherwise normal rats cause SC white matter lesions similar to those induced by Cbl deficiency. Cbl positively regulates SC PrPC synthesis in rat by stimulating the local synthesis of epidermal growth factor (EGF), which also induces the local synthesis of PrPC-mRNAs, and downregulating the local synthesis of tumor necrosis factor(TNF)-ï¡, thus preventing local PrPC overproduction. We have clinically demonstrated that PrPC levels are increased in the CSF of patients with subacute combined degeneration (SCD), unchanged in the CSF of patients with Alzheimer's disease and amyotrophic lateral sclerosis, and decreased in the CSF and SC of patients with multiple sclerosis (MS), regardless of its clinical course. We conclude that SCD (human and experimental) is a neurological disease due to excess PrPC without conformational change and aggregation, that the increase in PrPC levels in SCD and Cbl-D polyneuropathy and their decrease in MS CNS make them antipodian myelin diseases in terms of quantitative PrPC abnormalities, and that these abnormalities are related to myelin damage in the former, and impede myelin repair in the latter.