Functional Role of the Disulfide Isomerase ERp57 in Axonal Regeneration

• DOI: 10.1371/journal.pone.0136620
• Publication Date: 2015-09-11T14:04:09Z
• Authors: Valentina Castillo; Maritza Oñate; Ute Woehlbier; Pablo Rozas; Catherine Andreu; Danilo Medinas; Pamela Valdés; Fabiola Osorio; Gabriela Mercado; René L. Vidal; Bredford Kerr; Felipe A. Court; Claudio Hetz
• Keywords: Proteostasis; Calnexin; Peripheral Nervous System; Neurotoxin

ERp57 (also known as grp58 and PDIA3) is a protein disulfide isomerase that catalyzes bonds formation of glycoproteins part the calnexin calreticulin cycle. markedly upregulated in most common neurodegenerative diseases downstream endoplasmic reticulum (ER) stress response. Despite accumulating correlative evidence supporting neuroprotective role ERp57, contribution this foldase to physiology nervous system remains unknown. Here we developed transgenic mouse model overexpresses under control prion promoter. We analyzed susceptibility mice undergo neurodegeneration. Unexpectedly, overexpression did not affect dopaminergic neuron loss striatal denervation after injection Parkinson's disease-inducing neurotoxin. In sharp contrast, animals presented enhanced locomotor recovery mechanical injury sciatic nerve. These protective effects were associated with myelin removal, macrophage infiltration axonal regeneration. Our results suggest specifically contributes peripheral nerve regeneration, whereas its activity dispensable for survival specific neuronal population central system. demonstrate first time functional component ER proteostasis network