Neuroprotective Protein and Carboxypeptidase E

Abstract

This review outlines the neuroprotective activities and structural specificities of two distinct proteins, activity-dependent neuroprotective protein, a protein assigned transcription factor/chromatin remodeling activity, and carboxypeptidase E, a classic exopeptidase. Future studies will elucidate how these two versatile proteins converge onto a similar endpoint: neuroprotection.

The Molecular Profiles of Neural Stem Cell Niche in the Adult Subventricular Zone

“…However, an N-terminal truncated isoform of CPE (CPE-ΔN) was found to drive tumor progression in different types of cancer [88]. In the nervous system, CPE exerts its function in neuroprotection [89] and dendrite development [90], [91]. Our experiment showed that in the presence of recombinant CPE, fewer neurospheres were formed (p<0.0001) and the average neurosphere diameter was significantly smaller than the control (p = 0.031).…”

“…Such enzymatic-independent function of CPE could be achieved through receptor-mediated signaling. Based on the structural homology between the catalytic site within the amino-terminal domain of the Shh protein (Shh-N) and the catalytic site common to all carboxypeptidases, including CPE, it was speculated that CPE may work in a similar manner as a signaling molecule [89], but no experimental evidence has been reported. Alternatively, because CPE has a binding affinity for proteins other than pro-peptides [90], CPE may bind to selective proteins/peptides in the culture medium such as insulin or growth factors, thereby interfering with ligand-receptor interactions.…”

Carboxypeptidase E/NFα1: A New Neurotrophic Factor against Oxidative Stress-Induced Apoptotic Cell Death Mediated by ERK and PI3-K/AKT Pathways

“…Recent studies have suggested that carboxypeptidase E (CPE) is involved in neuroprotection [5]. CPE was first discovered as an enkephalin convertase in 1982 [6], [7] and was subsequently found to be the enzyme that cleaves the C-terminally extended basic residues from peptide intermediates in endocrine cells and neuropeptides in peptidergic neurons (for review see [8]).…”

“…Additionally, CPE-KO, but not WT mice exhibited neurodegeneration in the CA3 region of the hippocampus after weaning stress, which includes maternal separation, tail clipping for genotyping and ear tagging [17], [18]. Studies also showed that postnatal day 6 cultured cerebellar granule neurons from Cpe +/− mice with reduced CPE expression exhibited greater cell death after K + deprivation (5 mM) compared with Cpe +/+ mice [5]. Direct evidence of a neuroprotective role of CPE came from the study showing that transduction of CPE into primary cultured hippocampal neurons protected them against oxidative stress-induced cell death [17].…”

Carboxypeptidase E (NF-α1): a new trophic factor in neuroprotection

“…For example, primary cultured hippocampal neurons from CPE KO mice are more prone to die in culture than those from wild-type littermates [20] . Also, low-potassium-induced apoptosis is significantly increased in CPE +/ cerebellar granule neurons (CGNs) in comparison to CPE +/+ CGNs, indicating that CPE plays a neuroprotective role in this type of neuron as well as hippocampal neurons [21] . More direct evidence came from a study showing that transduction of an adenovirus carrying CPE into primary cultured hippocampal neurons, causing over-expression of CPE, protects against hydrogen peroxide-induced neurotoxicity [17] .…”