scholarly journals Differential Degradation of Amyloid β Genetic Variants Associated with Hereditary Dementia or Stroke by Insulin-degrading Enzyme

2003 ◽  
Vol 278 (26) ◽  
pp. 23221-23226 ◽  
Author(s):  
Laura Morelli ◽  
Ramiro Llovera ◽  
Silvia A. Gonzalez ◽  
José L. Affranchino ◽  
Frances Prelli ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Amyloid Β ◽  
Insulin Degrading Enzyme ◽  
Degrading Enzyme ◽  
Differential Degradation

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 Degradation of Alzheimer’s Amyloid-β by a Catalytically Inactive Insulin Degrading Enzyme

2020 ◽  
Author(s):  
Bikash R. Sahoo ◽  
Wenguang Liang ◽  
Wei-Jen Tang ◽  
Ayyalusamy Ramamoorthy
Keyword(s):  
High Speed ◽  
Amyloid Β ◽  
Insulin Degrading Enzyme ◽  
Degrading Enzyme ◽  
Diffusion Nmr ◽  
Zinc Removal ◽  
Aβ Aggregation ◽  
Aβ Degradation

AbstractInsulin-degrading-enzyme (IDE) is a key target to treat type-2 diabetes, and also known to clear Alzheimer’s amyloid-β (Aβ). However, the development of catalytically inactive IDE mutant (E111QIDE) could risk Aβ clearance. Here, we demonstrate Aβ degradation by E111QIDE and the removal of zinc from the toxic Aβ-Zn complex enabling proteolysis by IDE. Fluorescence and NMR results show delays in Aβ aggregation by both wild-type and E111QIDE in their zinc-bound and unbound states. Diffusion NMR and LC-MS revealed the delayed kinetics is due to Aβ degradation. Remarkably, IDEs exhibited no proteolysis against zinc bound Aβ species as evidenced from high-speed AFM, electron microscopy, chromatography and NMR. On the other hand, zinc removal from the Zn-Aβ complex enabled the proteolysis by IDEs. These findings highlight the role of zinc in switching on/off the proteolysis of Aβ and urge the development potent zinc chelators as a strategic alternative therapeutic for AD.Graphical abstract

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

scholarly journals The core sequence of PIF competes for insulin/amyloid β in insulin degrading enzyme: potential treatment for Alzheimer's disease

Oncotarget ◽  
2018 ◽  
Vol 9 (74) ◽  
pp. 33884-33895 ◽  
Author(s):  
Soren Hayrabedyan ◽  
Krassimira Todorova ◽  
Marialuigia Spinelli ◽  
Eytan R. Barnea ◽  
Martin Mueller
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
Potential Treatment ◽  
Insulin Degrading Enzyme ◽  
Degrading Enzyme ◽  
The Core ◽  
Core Sequence

Eicosapentaenoic acid and docosahexaenoic acid increase the degradation of amyloid-β by affecting insulin-degrading enzyme

2016 ◽  
Vol 94 (6) ◽  
pp. 534-542 ◽  
Author(s):  
Marcus O.W. Grimm ◽  
Janine Mett ◽  
Christoph P. Stahlmann ◽  
Viola J. Haupenthal ◽  
Tamara Blümel ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Docosahexaenoic Acid ◽  
Eicosapentaenoic Acid ◽  
Molecular Mechanisms ◽  
Amyloid Β ◽  
Proteolytic Processing ◽  
Omega 3 ◽  
Insulin Degrading Enzyme ◽  
Degrading Enzyme ◽  
Aβ Degradation

Omega-3 polyunsaturated fatty acids (PUFAs) have been proposed to be highly beneficial in Alzheimer’s disease (AD). AD pathology is closely linked to an overproduction and accumulation of amyloid-β (Aβ) peptides as extracellular senile plaques in the brain. Total Aβ levels are not only dependent on its production by proteolytic processing of the amyloid precursor protein (APP), but also on Aβ-clearance mechanisms, including Aβ-degrading enzymes. Here we show that the omega-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) increase Aβ-degradation by affecting insulin-degrading enzyme (IDE), the major Aβ-degrading enzyme secreted into the extracellular space of neuronal and microglial cells. The identification of the molecular mechanisms revealed that EPA directly increases IDE enzyme activity and elevates gene expression of IDE. DHA also directly stimulates IDE enzyme activity and affects IDE sorting by increasing exosome release of IDE, resulting in enhanced Aβ-degradation in the extracellular milieu. Apart from the known positive effect of DHA in reducing Aβ production, EPA and DHA might ameliorate AD pathology by increasing Aβ turnover.

Sign in / Sign up

Export Citation Format

Share Document