Abnormalities of peptide metabolism in Alzheimer disease.

Abstract

The steady-state level of peptide hormones represents a balance between their biosynthesis and proteolytic processing by convertases and their catabolism by proteolytic enzymes. Low levels of neuropeptide Y, somatostatin and corticotropin-releasing factor, described in Alzheimer disease (AD), were related to a defect in proteolytic processing of their protein precursors. In contrast the abundance of beta-amyloid peptides, the major protein constituents of senile plaques is likely related to inefficient catabolism. Therefore, attention is mainly focused on convertases that generate active peptides and counter-regulatory proteases that are involved in their catabolism. Some well-described proteases such as NEP are thought to be involved in beta-amyloid catabolism. The search of other possible candidates represents a primary effort in the field. A variety of vascular risk factors such as diabetes, hypertension and arteriosclerosis suggest that the functional vascular defect contributes to AD pathology. It has also been described that beta-amyloid peptides potentiate endothelin-1 induced vasoconstriction. In this review, we will critically evaluate evidence relating proteases implicated in amyloid protein precursor proteolytic processing and beta-amyloid catabolism.

• Authors: Maï Panchal, Mohamed Rholam, Noureddine Brakch
• Journal: Current neurovascular research (Curr Neurovasc Res) Vol. 1 Issue 4 Pg. 317-23 (Oct 2004) ISSN: 1567-2026 [Print] United Arab Emirates
• PMID: 16181081 (Publication Type: Journal Article, Review)

Chemical References

• Amyloid beta-Peptides
• Amyloid beta-Protein Precursor
• Endothelin-1
• Peptides
• Amyloid Precursor Protein Secretases
• Endopeptidases
• Peptide Hydrolases
• Aspartic Acid Endopeptidases
• BACE1 protein, human

Topics

• Alzheimer Disease (metabolism)
• Amyloid Precursor Protein Secretases
• Amyloid beta-Peptides (metabolism)
• Amyloid beta-Protein Precursor (metabolism)
• Animals
• Aspartic Acid Endopeptidases (classification, metabolism)
• Endopeptidases
• Endothelin-1 (pharmacology)
• Humans
• Models, Biological
• Peptide Hydrolases (metabolism)
• Peptides (metabolism)