Effects of Age and Retinal Degeneration on the Expression of Subtilisin-like Proprotein Convertases in the Visual Cortex of Mice

Abstract

Postnatal development of the visual cortex is a complex process that involves a number of molecules like growth factors, neuropeptides and cholesterol. Neurotrophins, like NGF, BDNF, NT-3, and NT-4, which are synthesized as precursors, also play a very important role in visual cortex development. Subtilisin-like proprotein convertases (SPCs) play a vital role in the limited endoproteolysis of precursors of secretory proteins that participate in development, homeostasis and in numerous pathologies. SPCs also process pro-neurotrophins into mature forms which facilitates neuron survival and differentiation through binding of the neurotrophins Trk receptors. In contrast, unprocessed forms of neurotrophins bind to the p75NTR death receptor and cause apoptosis. We studied the expression pattern of SPCs during postnatal development of the visual cortex in wild type mice (wt) and retinal degeneration mice (rd) using quantitative real-time PCR. The widely expressed SPCs showed a similar pattern of expression during development with high levels of mRNA early in postnatal development. The expression pattern of SPCs was total different in rd mice. Lower levels of expression of both widely expressed adn tissue-specific SPCs were seen at week 1. PCSK9 also showed a significant difference in expression. PCSK9 might play an important role in synaptic formation by regulating the uptake of cholesterol. This difference in expression pattern of SPCs during development and retinal degeneration support the hypothesis that SPCs play a critical role duirng brain development and nuerodegenerative diseases. Understanding the potential role of SPCs in neurdegenerative diseases may lead to new targets for treating such diseases.