The amyloid precursor protein (APP) and the angiotensin converting enzyme (ACE) secretase are inhibited by hydroxamic acid-based inhibitors

1998 ◽  
Vol 26 (3) ◽  
pp. S242-S242 ◽  
Author(s):  
S. Parvathy ◽  
Ishrut Hussain ◽  
Eric H. Karran ◽  
Anthony J. Turner ◽  
Nigel M. Hooper
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Amyloid Precursor Protein ◽  
Hydroxamic Acid ◽  
Precursor Protein ◽  
Converting Enzyme

scholarly journals A clinical dose of angiotensin-converting enzyme (ACE) inhibitor and heterozygous ACE deletion exacerbate Alzheimer's disease pathology in mice

2019 ◽  
Vol 294 (25) ◽  
pp. 9760-9770 ◽  
Author(s):  
Shuyu Liu ◽  
Fujiko Ando ◽  
Yu Fujita ◽  
Junjun Liu ◽  
Tomoji Maeda ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Angiotensin Converting Enzyme ◽  
Amyloid Precursor Protein ◽  
Ace Inhibitors ◽  
Ace Inhibitor ◽  
Precursor Protein ◽  
Causative Role ◽  
Converting Enzyme ◽  
Clinical Dose

Inhibition of angiotensin-converting enzyme (ACE) is a strategy used worldwide for managing hypertension. In addition to converting angiotensin I to angiotensin II, ACE also converts neurotoxic β-amyloid protein 42 (Aβ42) to Aβ40. Because of its neurotoxicity, Aβ42 is believed to play a causative role in the development of Alzheimer's disease (AD), whereas Aβ40 has neuroprotective effects against Aβ42 aggregation and also against metal-induced oxidative damage. Whether ACE inhibition enhances Aβ42 aggregation or impairs human cognitive ability are very important issues for preventing AD onset and for optimal hypertension management. In an 8-year longitudinal study, we found here that the mean intelligence quotient of male, but not female, hypertensive patients taking ACE inhibitors declined more rapidly than that of others taking no ACE inhibitors. Moreover, the sera of all AD patients exhibited a decrease in Aβ42-to-Aβ40–converting activity compared with sera from age-matched healthy individuals. Using human amyloid precursor protein transgenic mice, we found that a clinical dose of an ACE inhibitor was sufficient to increase brain amyloid deposition. We also generated human amyloid precursor protein/ACE+/− mice and found that a decrease in ACE levels promoted Aβ42 deposition and increased the number of apoptotic neurons. These results suggest that inhibition of ACE activity is a risk factor for impaired human cognition and for triggering AD onset.

Angiotensin converting enzyme and the amyloid precursor protein secretases

1999 ◽  
Vol 27 (1) ◽  
pp. A23-A23
Author(s):  
Nigel M. Hooper ◽  
S. Parvathy ◽  
Eric H. Karran ◽  
Anthony J. Turner
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Amyloid Precursor Protein ◽  
Precursor Protein ◽  
Converting Enzyme

scholarly journals The role of ADAM10 and ADAM17 in the ectodomain shedding of angiotensin converting enzyme and the amyloid precursor protein

2004 ◽  
Vol 271 (12) ◽  
pp. 2539-2547 ◽  
Author(s):  
Tobias M. J. Allinson ◽  
Edward T. Parkin ◽  
Thomas P. Condon ◽  
Sylva L. U. Schwager ◽  
Edward D. Sturrock ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Amyloid Precursor Protein ◽  
Precursor Protein ◽  
Ectodomain Shedding ◽  
Converting Enzyme

Angiotensin-converting enzyme and the amyloid precursor protein secretases

1999 ◽  
Vol 27 (2) ◽  
pp. 229-234 ◽  
Author(s):  
N. M. Hooper ◽  
S. Parvathy ◽  
E. H. Karran ◽  
A. J. Turner
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Amyloid Precursor Protein ◽  
Precursor Protein ◽  
Converting Enzyme

Protein processing mechanisms: from angiotensin-converting enzyme to Alzheimer's disease

2000 ◽  
Vol 28 (4) ◽  
pp. 441-446
Author(s):  
N. M. Hooper ◽  
A. J. Turner
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Angiotensin Converting Enzyme ◽  
Amyloid Precursor Protein ◽  
Neuronal Cell ◽  
Precursor Protein ◽  
Soluble Form ◽  
Converting Enzyme ◽  
A Disintegrin And Metalloproteinase ◽  
Factor Α

Angiotensin-converting enzyme (ACE) and the Alzheimer's disease amyloid precursor protein are two examples of membrane-bound proteins that are released in a soluble form by a post-trans-lational proteolytic cleavage event involving a secretase. Site-specific antibodies and matrix-assisted laser desorption ionization-time-of-flight (‘MALDI-TOF’) MS have been used to map the secretase cleavage site in somatic ACE to Arg-1203/Ser-1204, 24 residues proximal to the membrane-anchoring domain. Trypsin, which can solubilize ACE from the membrane, cleaves the protein at the same site. The use of structurally related hydroxamic acid-based zinc metalloproteinase inhibitors indicate that tumour necrosis factor-α convertase, a member of the ADAMs (‘a disintegrin and metalloproteinase’) family of proteins, is not involved in the proteolytic release of ACE, or in the constitutive or regulated α-secretase release of the amyloid precursor protein from a human neuronal cell line.

scholarly journals MicroRNA-298 and MicroRNA-328 Regulate Expression of Mouse β-Amyloid Precursor Protein-converting Enzyme 1

2008 ◽  
Vol 284 (4) ◽  
pp. 1971-1981 ◽  
Author(s):  
Vincent Boissonneault ◽  
Isabelle Plante ◽  
Serge Rivest ◽  
Patrick Provost
Keyword(s):  
Amyloid Precursor Protein ◽  
Precursor Protein ◽  
Converting Enzyme ◽  
Β Amyloid
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