IDE Gene - Insulin-Degrading Enzyme

IDE Gene

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">IDE Gene - Insulin-Degrading Enzyme</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>IDE</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>10q23.33</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>3416</td>
</tr>
<tr>
<td class="label">Protein</td>
<td>[Insulin-Degrading Enzyme](/entities/insulin-degrading-enzyme) (IDE)</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~110 kDa</td>
</tr>
<tr>
<td class="label">Function</td>
<td>Peptide hydrolysis, amyloid clearance</td>
</tr>
<tr>
<td class="label">Related Diseases</td>
<td>Alzheimer's Disease, Parkinson's Disease, Type 2 Diabetes</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/alzheimer" style="color:#ef9a9a">ALZHEIMER</a>, <a href="/wiki/alzheimer's-disease" style="color:#ef9a9a">ALZHEIMER'S DISEASE</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/carcinoma" style="color:#ef9a9a">Carcinoma</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">35 edges</a></td>
</tr>
</table>

Introduction

...

IDE Gene

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">IDE Gene - Insulin-Degrading Enzyme</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>IDE</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>10q23.33</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>3416</td>
</tr>
<tr>
<td class="label">Protein</td>
<td>[Insulin-Degrading Enzyme](/entities/insulin-degrading-enzyme) (IDE)</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~110 kDa</td>
</tr>
<tr>
<td class="label">Function</td>
<td>Peptide hydrolysis, amyloid clearance</td>
</tr>
<tr>
<td class="label">Related Diseases</td>
<td>Alzheimer's Disease, Parkinson's Disease, Type 2 Diabetes</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/alzheimer" style="color:#ef9a9a">ALZHEIMER</a>, <a href="/wiki/alzheimer's-disease" style="color:#ef9a9a">ALZHEIMER'S DISEASE</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/carcinoma" style="color:#ef9a9a">Carcinoma</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">35 edges</a></td>
</tr>
</table>

Introduction

Ide Gene Insulin Degrading Enzyme is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Overview

The IDE (Insulin-Degrading Enzyme) gene encodes a ubiquitously expressed thiol metalloprotease that degrades insulin, [amyloid-beta](/proteins/amyloid-beta), and other peptides. IDE plays critical roles in metabolism and proteostasis, with particular relevance to Alzheimer's disease and diabetes. Located on chromosome 10q23.33, IDE has been extensively studied for its role in clearing amyloid-beta peptides and its potential as a therapeutic target for neurodegenerative diseases. [@kurochkin1994]

This gene is involved in: [@styczynski2010]

• Amyloid-beta degradation: Primary enzyme responsible for clearing Abeta in the brain
• Insulin metabolism: Regulates insulin signaling through peptide degradation
• Proteostasis: Maintains cellular protein quality control
• Disease associations: Alzheimer's disease, Parkinson's disease, Type 2 diabetes

IDE (Insulin-Degrading Enzyme), also known as insulysin, is a gene encoding a ubiquitously expressed thiol metalloprotease that degrades insulin, [amyloid-beta](/proteins/amyloid-beta), and other peptides. It plays critical roles in metabolism and proteostasis, with particular relevance to Alzheimer's disease and diabetes. The IDE gene has been extensively studied for its role in clearing amyloid-beta peptides and its potential as a therapeutic target for neurodegenerative diseases. [@vepsalainen2014]

Gene Overview

Molecular Function

IDE is a zinc-dependent metallopeptidase consisting of 1019 amino acids that performs several critical functions in cellular proteostasis:

Substrate Specificity

IDE degrades a wide range of peptide substrates:

• Insulin: Primary physiological substrate, regulating insulin signaling
• Amylin: Islet amyloid polypeptide co-secreted with insulin
• Glucagon: Pancreatic hormone regulating glucose metabolism
• Atrial Natriuretic Peptide: Cardiovascular regulatory peptide
• Amyloid-beta (Aβ): Key substrate in Alzheimer's disease pathogenesis
• [α-Synuclein](/proteins/alpha-synuclein): Parkinson's disease-related protein
• Islet Amyloid Polypeptide (IAPP): Amyloidogenic peptide in type 2 diabetes

Catalytic Mechanism

IDE exhibits unique enzymatic properties:

• Allosteric regulation by substrate binding
• Cooperative kinetics with insulin
• Ability to degrade oligomeric and fibrillar aggregates
• ATP-independent proteolysis
• Broad pH optimum spanning physiological and acidic conditions

Role in Neurodegeneration

Alzheimer's Disease

IDE plays a critical role in Alzheimer's disease pathogenesis:

• Primary Aβ-degrading enzyme: IDE is the major enzyme responsible for clearing Aβ in the brain
• IDE deficiency consequences: IDE knockout mice accumulate Aβ and develop cognitive deficits
• Genetic associations: IDE polymorphisms modify AD risk and age of onset
• Expression changes: Reduced IDE expression observed in AD brains
• IDE-Aβ complexes: Detectable in cerebrospinal fluid of AD patients
• Therapeutic potential: Enhancing IDE activity could reduce Aβ burden

Parkinson's Disease

IDE involvement in Parkinson's disease includes:

• α-Synuclein degradation: IDE can degrade monomeric α-synuclein
• Activity reduction: IDE activity is reduced in PD brains
• Genetic associations: IDE promoter variants associated with PD risk
• Diabetes-PD link: Shared metabolic pathways may involve IDE dysfunction

Diabetes Connection

The connection between type 2 diabetes and neurodegenerative diseases:

• Type 2 Diabetes: IDE variants increase risk for both T2D and AD
• Insulin signaling: IDE regulates insulin signaling pathways
• Shared pathways: Metabolic dysfunction links T2D and neurodegeneration
• Type 3 Diabetes hypothesis: Proposes AD as a form of brain diabetes

Expression Pattern

IDE is ubiquitously expressed throughout the body:

• Brain: [Neurons](/entities/neurons) and glia, highest in [hippocampus](/brain-regions/hippocampus) and [cortex](/brain-regions/cortex)
• Pancreas: Beta cells of the islets of Langerhans
• Liver: Hepatocytes
• Muscle: Skeletal muscle tissue
• Adipose: Adipose tissue
• Kidney: Renal tubular cells

Genetic Variation

Known Polymorphisms

Several IDE variants have been associated with disease risk:

• SNP variants in promoter region affecting expression
• Variants in coding region potentially altering enzyme activity
• Linkage disequilibrium with nearby genes (e.g., CR2)

Association Studies

• IDE variants associated with increased AD risk
• Some variants protective against Aβ accumulation
• Gender-specific effects observed in some studies

Therapeutic Strategies

IDE Enhancers

Compounds that increase IDE expression or activity:

• Small molecule activators identified through screening
• Natural compounds (e.g., certain flavonoids)
• Proteasome inhibitors increasing IDE stability

Allosteric Modulators

Targeting IDE's unique substrate-binding site:

• Compounds enhancing IDE-Aβ interactions
• Allosteric activators improving catalytic efficiency

Gene Therapy Approaches

• AAV-mediated IDE delivery to brain
• Viral vector transduction for sustained IDE expression
• Cell-based therapy using IDE-overexpressing cells

Combination Therapy

Rational combinations for enhanced efficacy:

• IDE activators combined with Aβ-targeting antibodies
• IDE enhancers with BACE inhibitors
• Multi-target approaches addressing proteostasis

Background

The study of Ide Gene Insulin Degrading Enzyme has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

Brain Atlas Resources

• [Allen Human Brain Atlas - ide Expression](https://human.brain-map.org/microarray/search/show?search_term=ide)
• [Allen Cell Type Atlas - ide](https://celltypes.brain-map.org/)
• [BrainSpan - ide Developmental Expression](https://brainspan.org/)
• [Allen Mouse Brain Atlas - ide](https://mouse.brain-map.org/)

See Also

• [IDE Protein](/proteins/ide-protein)
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• [Protein Quality Control Network](/mechanisms/protein-quality-control)
• - [Amyloid Cascade Pathway](/mechanisms/amyloid-cascade-hypothesis)
• [Brain Insulin Signaling](/mechanisms/brain-insulin-signaling)

Pathway Diagram

The following diagram shows the key molecular relationships involving IDE Gene - Insulin-Degrading Enzyme discovered through SciDEX knowledge graph analysis: