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6 February 2001. The enzyme neprilysin-capable of degrading Aβ42
peptide-is a new
player in the Alzheimer's disease mystery. Writing in Neuroscience
Letters, Patrick McGeer's group at the University of British Columbia
adds critical circumstantial evidence that places neprilysin at the
scene of neurodegeneration. Neprilysin (alias neural endopeptidase,
EC3.4.24.11, enkephalinase, CD10, or common acute lymphblastic leukemia
antigen [CALLA]) cleaves enkephalins, endorphins, substance P, and other
small peptides throughout the body. Recent animal data show that when
neprilysin is inhibited, amyloid deposits can build up quickly. The
suggestion has been made that compromised neprilysin-mediated scavenging
of Aβ is important to the final pathology of Alzheimer's.
McGeer and colleagues compared neprilysin mRNA and protein levels in
postmortem human brain and other organs of AD and control cases. Within
both study groups, the hippocampus and temporal gyrus, areas susceptible
to plaques, showed particularly low levels of neprilysin mRNA.
Conversely, the caudate and peripheral organs that are resistant to
plaque formation had the highest levels of neprilysin mRNA. Compared to
controls, neprilysin mRNA levels in AD brains were much lower in
hippocampus and midtemporal gyrus, but not in other areas. Similar
patterns was found for the protein product.
"If the human brain depends upon neprilysin as the main enzyme to break
down Aβ, then the data reported here would help to explain why areas
such as the hippocampus and temporal gyrus are highly vulnerable to
plaque formation," write the authors. "They would also help to explain
why Aβ deposits do not appear in peripheral organs but are confined
to restricted regions of the brain."-Hakon Heimer.
Reference:
Yasojima K, Akiyama H, McGeer EG, McGeer PL. Reduced neprilysin in high plaque areas of Alzheimer brain: a possible relationship to deficient degradation of beta-amyloid peptide. Neurosci Lett 2001 Jan 12;297:97-100. Abstract
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