Acyl peptide hydrolase degrades monomeric and oligomeric amyloid-beta peptide
<p>Abstract</p> <p>Background</p> <p>The abnormal accumulation of amyloid-beta peptide is believed to cause malfunctioning of neurons in the Alzheimer's disease brain. Amyloid-beta exists in different assembly forms in the aging mammalian brain including monomers,...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2009-07-01
|
| Series: | Molecular Neurodegeneration |
| Online Access: | http://www.molecularneurodegeneration.com/content/4/1/33 |
| _version_ | 1818790917525471232 |
|---|---|
| author | O'Connor Peter B Zhao Cheng Yamin Rina McKee Ann C Abraham Carmela R |
| author_facet | O'Connor Peter B Zhao Cheng Yamin Rina McKee Ann C Abraham Carmela R |
| author_sort | O'Connor Peter B |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>The abnormal accumulation of amyloid-beta peptide is believed to cause malfunctioning of neurons in the Alzheimer's disease brain. Amyloid-beta exists in different assembly forms in the aging mammalian brain including monomers, oligomers, and aggregates, and in senile plaques, fibrils. Recent findings suggest that soluble amyloid-beta oligomers may represent the primary pathological species in Alzheimer's disease and the most toxic form that impairs synaptic and thus neuronal function. We previously reported the isolation of a novel amyloid-beta-degrading enzyme, acyl peptide hydrolase, a serine protease that degrades amyloid-beta, and is different in structure and activity from other amyloid-beta-degrading enzymes.</p> <p>Results</p> <p>Here we report the further characterization of acyl peptide hydrolase activity using mass spectrometry. Acyl peptide hydrolase cleaves the amyloid-beta peptide at amino acids 13, 14 and 19. In addition, by real-time PCR we found elevated acyl peptide hydrolase expression in brain areas rich in amyloid plaques suggesting that this enzyme's levels are responsive to increases in amyloid-beta levels. Lastly, tissue culture experiments using transfected CHO cells expressing APP751 bearing the V717F mutation indicate that acyl peptide hydrolase preferentially degrades dimeric and trimeric forms of amyloid-beta.</p> <p>Conclusion</p> <p>These data suggest that acyl peptide hydrolase is involved in the degradation of oligomeric amyloid-beta, an activity that, if induced, might present a new tool for therapy aimed at reducing neurodegeneration in the Alzheimer's brain.</p> |
| first_indexed | 2024-12-18T15:03:04Z |
| format | Article |
| id | doaj.art-3f3d08dd0d9a43baa20fbf4d478c577f |
| institution | Directory Open Access Journal |
| issn | 1750-1326 |
| language | English |
| last_indexed | 2024-12-18T15:03:04Z |
| publishDate | 2009-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Neurodegeneration |
| spelling | doaj.art-3f3d08dd0d9a43baa20fbf4d478c577f2022-12-21T21:03:51ZengBMCMolecular Neurodegeneration1750-13262009-07-01413310.1186/1750-1326-4-33Acyl peptide hydrolase degrades monomeric and oligomeric amyloid-beta peptideO'Connor Peter BZhao ChengYamin RinaMcKee Ann CAbraham Carmela R<p>Abstract</p> <p>Background</p> <p>The abnormal accumulation of amyloid-beta peptide is believed to cause malfunctioning of neurons in the Alzheimer's disease brain. Amyloid-beta exists in different assembly forms in the aging mammalian brain including monomers, oligomers, and aggregates, and in senile plaques, fibrils. Recent findings suggest that soluble amyloid-beta oligomers may represent the primary pathological species in Alzheimer's disease and the most toxic form that impairs synaptic and thus neuronal function. We previously reported the isolation of a novel amyloid-beta-degrading enzyme, acyl peptide hydrolase, a serine protease that degrades amyloid-beta, and is different in structure and activity from other amyloid-beta-degrading enzymes.</p> <p>Results</p> <p>Here we report the further characterization of acyl peptide hydrolase activity using mass spectrometry. Acyl peptide hydrolase cleaves the amyloid-beta peptide at amino acids 13, 14 and 19. In addition, by real-time PCR we found elevated acyl peptide hydrolase expression in brain areas rich in amyloid plaques suggesting that this enzyme's levels are responsive to increases in amyloid-beta levels. Lastly, tissue culture experiments using transfected CHO cells expressing APP751 bearing the V717F mutation indicate that acyl peptide hydrolase preferentially degrades dimeric and trimeric forms of amyloid-beta.</p> <p>Conclusion</p> <p>These data suggest that acyl peptide hydrolase is involved in the degradation of oligomeric amyloid-beta, an activity that, if induced, might present a new tool for therapy aimed at reducing neurodegeneration in the Alzheimer's brain.</p>http://www.molecularneurodegeneration.com/content/4/1/33 |
| spellingShingle | O'Connor Peter B Zhao Cheng Yamin Rina McKee Ann C Abraham Carmela R Acyl peptide hydrolase degrades monomeric and oligomeric amyloid-beta peptide Molecular Neurodegeneration |
| title | Acyl peptide hydrolase degrades monomeric and oligomeric amyloid-beta peptide |
| title_full | Acyl peptide hydrolase degrades monomeric and oligomeric amyloid-beta peptide |
| title_fullStr | Acyl peptide hydrolase degrades monomeric and oligomeric amyloid-beta peptide |
| title_full_unstemmed | Acyl peptide hydrolase degrades monomeric and oligomeric amyloid-beta peptide |
| title_short | Acyl peptide hydrolase degrades monomeric and oligomeric amyloid-beta peptide |
| title_sort | acyl peptide hydrolase degrades monomeric and oligomeric amyloid beta peptide |
| url | http://www.molecularneurodegeneration.com/content/4/1/33 |
| work_keys_str_mv | AT oconnorpeterb acylpeptidehydrolasedegradesmonomericandoligomericamyloidbetapeptide AT zhaocheng acylpeptidehydrolasedegradesmonomericandoligomericamyloidbetapeptide AT yaminrina acylpeptidehydrolasedegradesmonomericandoligomericamyloidbetapeptide AT mckeeannc acylpeptidehydrolasedegradesmonomericandoligomericamyloidbetapeptide AT abrahamcarmelar acylpeptidehydrolasedegradesmonomericandoligomericamyloidbetapeptide |