Aged PrP null mice show defective processing of neuregulins in the peripheral nervous system

作者：Benvegnu Stefano; Gasperini Lisa; Legname Giuseppe^*

来源：Molecular and Cellular Neuroscience, 2011, 47(1): 28-35.

DOI：10.1016/j.mcn.2011.02.005

• Prion protein
• Neuregulin
• Aging
• Nervous system

A prion, a protease-resistant conformer of the cellular prion protein (PrP(C)), is the causative agent of transmissible spongiform encephalopathies or prion diseases. While this property is well established for the aberrantly folded protein, the physiological function of PrP(C) remains elusive. Among different putative functions, the non-pathogenic protein isoform PrP(C) is involved in several cellular processes. Here, we show that PrP(C) regulates the cleavage of neuregulin-1 proteins (NRG1). Neuregulins provide key axonal signals that regulate several processes, including glial cells proliferation, survival and myelination. Interestingly, mice devoid of PrP(C) (Prnp(0/0)) were recently shown to have a late-onset demyelinating disease in the peripheral nervous system (PNS) but not in the central nervous system (CNS). We found that NRG1 processing is developmentally regulated in the PNS and, by comparing wildtype and Prnp(0/0) mice, that PrP(C) influences NRG1 processing in old, but not in young, animals. In addition, we found that also the processing of neuregulin-3, another neuregulin family member, is altered in the PNS of Prnp(0/0) mice. These differ

• 出版日期2011-5