Quantitative NMR Study of Insulin-Degrading Enzyme Using Amyloid-β and HIV-1 p6 Elucidates Its Chaperone Activity

Biochemistry ◽  
2021 ◽  
Author(s):  
Bhargavi Ramaraju ◽  
Spencer L. Nelson ◽  
Wenwei Zheng ◽  
Rodolfo Ghirlando ◽  
Lalit Deshmukh
Keyword(s):  
Amyloid Β ◽  
Chaperone Activity ◽  
Insulin Degrading Enzyme ◽  
Quantitative Nmr ◽  
Degrading Enzyme ◽  
Nmr Study ◽  
Hiv 1

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 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

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
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