Axonal prion protein is required for peripheral myelin maintenance

作者：Bremer Juliane; Baumann Frank; Tiberi Cinzia; Wessig Carsten; Fischer Heike; Schwarz Petra; Steele Andrew D; Toyka Klaus V; Nave Klaus Armin; Weis Joachim; Aguzzi Adriano^*

来源：Nature Neuroscience, 2010, 13(3): 310-U9.

DOI：10.1038/nn.2483

The integrity of peripheral nerves relies on communication between axons and Schwann cells. The axonal signals that ensure myelin maintenance are distinct from those that direct myelination and are largely unknown. Here we show that ablation of the prion protein PrPC triggers a chronic demyelinating polyneuropathy (CDP) in four independently targeted mouse strains. Ablation of the neighboring Prnd locus, or inbreeding to four distinct mouse strains, did not modulate the CDP. CDP was triggered by depletion of PrPC specifically in neurons, but not in Schwann cells, and was suppressed by PrPC expression restricted to neurons but not to Schwann cells. CDP was prevented by PrPC variants that undergo proteolytic amino-proximal cleavage, but not by variants that are nonpermissive for cleavage, including secreted PrPC lacking its glycolipid membrane anchor. These results indicate that neuronal expression and regulated proteolysis of PrPC are essential for myelin maintenance.

• 出版日期2010-3