Alternative Splicing of Human Insulin-Degrading Enzyme Yields a Novel Isoform with a Decreased Ability To Degrade Insulin and Amyloid β-Protein†

Biochemistry ◽  
2005 ◽  
Vol 44 (17) ◽  
pp. 6513-6525 ◽  
Author(s):  
Wesley Farris ◽  
Malcolm A. Leissring ◽  
Matthew L. Hemming ◽  
Alice Y. Chang ◽  
Dennis J. Selkoe
Keyword(s):  
Alternative Splicing ◽  
Human Insulin ◽  
Amyloid Β ◽  
Amyloid Β Protein ◽  
Insulin Degrading Enzyme ◽  
Degrading Enzyme ◽  
Β Protein

scholarly journals Purified recombinant insulin-degrading enzyme degrades amyloid β-protein but does not promote its oligomerization

2000 ◽  
Vol 351 (2) ◽  
pp. 509 ◽  
Author(s):  
Valérie CHESNEAU ◽  
Konstantinos VEKRELLIS ◽  
Marsha Rich ROSNER ◽  
Dennis J. SELKOE
Keyword(s):  
Amyloid Β ◽  
Amyloid Β Protein ◽  
Insulin Degrading Enzyme ◽  
Degrading Enzyme ◽  
Β Protein ◽  
Recombinant Insulin

scholarly journals Neurons Regulate Extracellular Levels of Amyloid β-Protein via Proteolysis by Insulin-Degrading Enzyme

2000 ◽  
Vol 20 (5) ◽  
pp. 1657-1665 ◽  
Author(s):  
Konstantinos Vekrellis ◽  
Zhen Ye ◽  
Wei Qiao Qiu ◽  
Dominic Walsh ◽  
Dean Hartley ◽  
...  
Keyword(s):  
Amyloid Β ◽  
Amyloid Β Protein ◽  
Insulin Degrading Enzyme ◽  
Degrading Enzyme ◽  
Β Protein

Insulin degrading enzyme (IDE): implications for the degradation and neurotoxicity of the amyloid β-protein

2000 ◽  
Vol 21 ◽  
pp. 115
Author(s):  
Konstantinos Vekrellis ◽  
Valerie Chesneau ◽  
Zhen Ye ◽  
Stefan Mansourian ◽  
Marsha . Rosner ◽  
...  
Keyword(s):  
Amyloid Β ◽  
Amyloid Β Protein ◽  
Insulin Degrading Enzyme ◽  
Degrading Enzyme ◽  
Β Protein

scholarly journals Purified recombinant insulin-degrading enzyme degrades amyloid β-protein but does not promote its oligomerization

2000 ◽  
Vol 351 (2) ◽  
pp. 509-516 ◽  
Author(s):  
Valérie CHESNEAU ◽  
Konstantinos VEKRELLIS ◽  
Marsha Rich ROSNER ◽  
Dennis J. SELKOE
Keyword(s):  
Culture Media ◽  
Degradation Products ◽  
Amyloid Β ◽  
Amyloid Β Protein ◽  
Insulin Degrading Enzyme ◽  
Degrading Enzyme ◽  
Β Protein ◽  
Recombinant Insulin ◽  
Molecular Masses

Amyloid β-protein (Aβ) has been implicated as an early and essential factor in the pathogenesis of Alzheimer's disease. Although its cellular production has been studied extensively, little is known about Aβ clearance. Recently, insulin-degrading enzyme (IDE), a 110-kDa metalloendopeptidase, was found to degrade both endogenously secreted and synthetic Aβ peptides. Surprisingly, IDE-mediated proteolysis of [125I]Aβ(1-40) in microglial cell-culture media was accompanied by the formation of 125I-labelled peptides with higher apparent molecular masses, raising the possibility that the degradation products act as ‘seeds’ for Aβ oligomerization. To directly address the role of IDE in Aβ degradation and oligomerization, we investigated the action of purified recombinant wild-type and catalytically inactive IDEs. Our data demonstrate that (i) IDE alone is sufficient to cleave purified Aβ that is either unlabelled, iodinated or 35S-labelled; (ii) the initial cleavage sites are His14–Gln15, Phe19–Phe20 and Phe20–Ala21; and (iii) incubation of IDE with [125I]Aβ, but not with [35S]-Aβ, leads to the formation of slower migrating species on gels. Since iodination labels N-terminal fragments of Aβ, and 35S labels C-terminal products, we analysed unlabelled synthetic fragments of Aβ and determined that only the N-terminal fragments migrate with anomalously high molecular mass. These results indicate that IDE alone is sufficient to degrade Aβ at specific sites, and that its degradation products do not promote oligomerization of the intact Aβ peptide.

scholarly journals Partial Loss-of-Function Mutations in Insulin-Degrading Enzyme that Induce Diabetes also Impair Degradation of Amyloid β-Protein

2004 ◽  
Vol 164 (4) ◽  
pp. 1425-1434 ◽  
Author(s):  
Wesley Farris ◽  
Stefan Mansourian ◽  
Malcolm A. Leissring ◽  
Elizabeth A. Eckman ◽  
Lars Bertram ◽  
...  
Keyword(s):  
Amyloid Β ◽  
Amyloid Β Protein ◽  
Loss Of Function ◽  
Insulin Degrading Enzyme ◽  
Partial Loss ◽  
Degrading Enzyme ◽  
Β Protein

scholarly journals Insulin-degrading Enzyme Regulates Extracellular Levels of Amyloid β-Protein by Degradation

1998 ◽  
Vol 273 (49) ◽  
pp. 32730-32738 ◽  
Author(s):  
Wei Qiao Qiu ◽  
Dominic M. Walsh ◽  
Zhen Ye ◽  
Konstantinos Vekrellis ◽  
Jimin Zhang ◽  
...  
Keyword(s):  
Amyloid Β ◽  
Amyloid Β Protein ◽  
Insulin Degrading Enzyme ◽  
Degrading Enzyme ◽  
Β Protein

scholarly journals The novel mitochondrial matrix protease Ste23 is required for efficient presequence degradation and processing

2017 ◽  
Vol 28 (8) ◽  
pp. 997-1002 ◽  
Author(s):  
Asli Aras Taskin ◽  
Cansu Kücükköse ◽  
Nils Burger ◽  
Dirk Mossmann ◽  
Chris Meisinger ◽  
...  
Keyword(s):  
Human Insulin ◽  
Feedback Inhibition ◽  
Amyloid Β ◽  
The Novel ◽  
Mitochondrial Matrix ◽  
Insulin Degrading Enzyme ◽  
Degrading Enzyme ◽  
Precursor Proteins ◽  
The Matrix ◽  
Processing Protease

Approximately 70% of mitochondrial precursor proteins are imported from the cytosol via N-terminal presequences, which are cleaved upon exposure to the mitochondrial processing protease MPP in the matrix. Cleaved presequence peptides then need to be efficiently degraded, and impairment of this clearance step, for example, by amyloid β peptides, causes feedback inhibition of MPP, leading ultimately to accumulation of immature precursor proteins within mitochondria. Degradation of mitochondrial peptides is performed by Cym1 in yeast and its homologue, PreP, in humans. Here we identify the novel mitochondrial matrix protease Ste23 in yeast, a homologue of human insulin-degrading enzyme, which is required for efficient peptide degradation. Ste23 and Cym1 tightly cooperate to ensure the correct functioning of the essential presequence processing machinery.

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