p(HGNC:IDE)
In a study reported by Kalinin et al., treatment of 5xFAD mice with the PPAR-d agonist, GW742, resulted in decreased plaque burden and an increase in the expression of two Ab proteases, neprilysin and IDE [72]. PubMed:21718217
In regard to pharmacological manipulation, substances such as epigallocatechin and somatostatin promote the expression, secretion and (allosterically) catalytic activ- ity of IDE and neprilysin in parallel with an increase in the degradation of Aβ peptides 259,280 . PubMed:30116051
In a vicious circle, Aβ42 itself decreases IDE expression, although it may prompt its release from glia 254,259 . PubMed:30116051
In regard to pharmacological manipulation, substances such as epigallocatechin and somatostatin promote the expression, secretion and (allosterically) catalytic activ- ity of IDE and neprilysin in parallel with an increase in the degradation of Aβ peptides 259,280 . PubMed:30116051
In regard to pharmacological manipulation, substances such as epigallocatechin and somatostatin promote the expression, secretion and (allosterically) catalytic activ- ity of IDE and neprilysin in parallel with an increase in the degradation of Aβ peptides 259,280 . PubMed:30116051
In regard to pharmacological manipulation, substances such as epigallocatechin and somatostatin promote the expression, secretion and (allosterically) catalytic activ- ity of IDE and neprilysin in parallel with an increase in the degradation of Aβ peptides 259,280 . PubMed:30116051
In regard to pharmacological manipulation, substances such as epigallocatechin and somatostatin promote the expression, secretion and (allosterically) catalytic activ- ity of IDE and neprilysin in parallel with an increase in the degradation of Aβ peptides 259,280 . PubMed:30116051
In regard to pharmacological manipulation, substances such as epigallocatechin and somatostatin promote the expression, secretion and (allosterically) catalytic activ- ity of IDE and neprilysin in parallel with an increase in the degradation of Aβ peptides 259,280 . PubMed:30116051
Cerebral levels of IDE are reduced in early AD and in mouse models of AD, whereas, mirroring AD amyloidosis, Aβ42 accumulates in mice genetically depleted of IDE. PubMed:30116051
For example, eicosapentaenoic acid (EPA) can induce the activity of IDE and increase its gene expression, and docosahexaenoic acid (DHA) also directly elevates IDE activity and affects sorting by boosting exosome release of IDE (Grimm et al. 2016) PubMed:29626319
For example, eicosapentaenoic acid (EPA) can induce the activity of IDE and increase its gene expression, and docosahexaenoic acid (DHA) also directly elevates IDE activity and affects sorting by boosting exosome release of IDE (Grimm et al. 2016) PubMed:29626319
Somatotatin also up-regulates the expression and secretion of IDE in order to enhance Aβ clearance (Tundo et al.2012) PubMed:29626319
Statin can lead to extracellular IDE secretion from astrocytes in an autophagy-based unconventional secretory pathway (Glebov and Walter 2012), thus enhancing the extracellular removal of Aβ PubMed:29626319
Meanwhile, an animal experiment showed that IDE expression will descend with age and diabetes, then resulting in Aβ deposition (Kochkina et al. 2015) PubMed:29626319
Meanwhile, an animal experiment showed that IDE expression will descend with age and diabetes, then resulting in Aβ deposition (Kochkina et al. 2015) PubMed:29626319
In Alzheimer disease, 66 genes were identified that are also modulated by Protandim at the gene expression level. Of these 66 genes, the first 43 of them (65%) were regulated by Protandim in the opposing direction to that taken by the Alzheimer disease process. The beneficial effect of Protandim is further supported by the fact that of the 10 gene products currently targeted by drug therapies, eight of them are modulated by Protandim in the same direction that is proposed to be beneficial and caused by the drug. PubMed:22020111
In Alzheimer disease, 66 genes were identified that are also modulated by Protandim at the gene expression level. Of these 66 genes, the first 43 of them (65%) were regulated by Protandim in the opposing direction to that taken by the Alzheimer disease process. The beneficial effect of Protandim is further supported by the fact that of the 10 gene products currently targeted by drug therapies, eight of them are modulated by Protandim in the same direction that is proposed to be beneficial and caused by the drug. PubMed:22020111
They were able to show that the lipidation of ApoE enhanced the degradation of soluble species of Ab by neprilysin in the endolytic compartments of microglia as well as extracellularly through the actions of the insulindegrading enzyme (IDE) [13]. PubMed:21718217
Aβ42 and amylin (a pancreas-derived, AD-associated protein found in brain) are substrates for degradation by IDE, which also irreversibly traps Aβ42 and α-synuclein, preventing their aggregation and promoting ALN and UPS elimination 259 . PubMed:30116051
Aβ42 and amylin (a pancreas-derived, AD-associated protein found in brain) are substrates for degradation by IDE, which also irreversibly traps Aβ42 and α-synuclein, preventing their aggregation and promoting ALN and UPS elimination 259 . PubMed:30116051
Aβ42 and amylin (a pancreas-derived, AD-associated protein found in brain) are substrates for degradation by IDE, which also irreversibly traps Aβ42 and α-synuclein, preventing their aggregation and promoting ALN and UPS elimination 259 . PubMed:30116051
Aβ42 and amylin (a pancreas-derived, AD-associated protein found in brain) are substrates for degradation by IDE, which also irreversibly traps Aβ42 and α-synuclein, preventing their aggregation and promoting ALN and UPS elimination 259 . PubMed:30116051
IDE also degrades and prevents the forma- tion of α-synuclein fibrils 259 . PubMed:30116051
Extracellular Aβ can also be degraded by proteases, such as neprily- sin (a membrane-anchored zinc metalloendopeptidase that degrades the Aβ monomers Aβ1-40 and Aβ1-42, and Aβ oligomers),119 matrix metalloproteinases 2, 3 and 9,120 glutamate carboxypeptidase II,121 endothelin-converting enzyme,122 tissue plasminogen activator,123 plasmin,120 angiotensin-converting enzyme,120 and insulin-degrading enzyme. PubMed:26195256
Extracellular Aβ degrading enzymes include neprilysin (NEP), insulin-degrading enzyme (IDE), matrix metalloproteinases (MMPs), angiotensin converting enzyme (ACE), endothelin-converting enzyme (ECE), and plasmin (Baranello et al. 2015) PubMed:29626319
IDE, a zinc endopeptidase, can degrade extracellular Aβ (Vekrellis et al. 2000) PubMed:29626319
Exercise training can increase extracellular Aβ clearance in the brains of Tg2576 mice in a dose-dependent manner through up-regulating NEP, IDE, MMP9, LRP1, and HSP70 (Moore et al. 2016) PubMed:29626319
Meanwhile, an animal experiment showed that IDE expression will descend with age and diabetes, then resulting in Aβ deposition (Kochkina et al. 2015) PubMed:29626319
Meanwhile, an animal experiment showed that IDE expression will descend with age and diabetes, then resulting in Aβ deposition (Kochkina et al. 2015) PubMed:29626319
The combined effect of the increased IDE production and phagocytic Abeta clearance reduced the cerebral Abeta load substantially, even at late life. Since immunohistochemistry found NLRP3 exclusively expressed in microglial cells, it has been concluded that the observed changes were entirely due to NLRP3 inflammasome modulation in these cells PubMed:28019679
The combined effect of the increased IDE production and phagocytic Abeta clearance reduced the cerebral Abeta load substantially, even at late life. Since immunohistochemistry found NLRP3 exclusively expressed in microglial cells, it has been concluded that the observed changes were entirely due to NLRP3 inflammasome modulation in these cells PubMed:28019679
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