PIK3R1 Gene

PIK3R1 Gene

Overview

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">PIK3R1 Gene</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>PIK3R1</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Phosphoinositide-3-Kinase Regulatory Subunit 1</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>5q13.1</td>
</tr>
<tr>
<td class="label">Protein Class</td>
<td>PI3K regulatory subunit (SH2 domain-containing)</td>
</tr>
<tr>
<td class="label">Aliases</td>
<td>p85α, PI3K-p85, GRB1</td>
</tr>
<tr>
<td class="label">Interactor</td>
<td>Interaction Type</td>
</tr>
<tr>
<td class="label">PIK3CA (p110α)</td>
<td>Catalytic subunit</td>
</tr>
<tr>
<td class="label">PTEN</td>
<td>Negative regulator</td>
</tr>
<tr>
<td class="label">IRS1/2</td>
<td>Substrate</td>
</tr>
<tr>
<td class="label">GRB2</td>
<td>Adapter protein</td>
</tr>
<tr>
<td class="label">Akt1/PKB</td>
<td>Downstream kinase</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/atherosclerosis" style="color:#ef9a9a">Atherosclerosis</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">232 edges</a></td>
</tr>
</table>

PIK3R1 Gene

Overview

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">PIK3R1 Gene</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>PIK3R1</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Phosphoinositide-3-Kinase Regulatory Subunit 1</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>5q13.1</td>
</tr>
<tr>
<td class="label">Protein Class</td>
<td>PI3K regulatory subunit (SH2 domain-containing)</td>
</tr>
<tr>
<td class="label">Aliases</td>
<td>p85α, PI3K-p85, GRB1</td>
</tr>
<tr>
<td class="label">Interactor</td>
<td>Interaction Type</td>
</tr>
<tr>
<td class="label">PIK3CA (p110α)</td>
<td>Catalytic subunit</td>
</tr>
<tr>
<td class="label">PTEN</td>
<td>Negative regulator</td>
</tr>
<tr>
<td class="label">IRS1/2</td>
<td>Substrate</td>
</tr>
<tr>
<td class="label">GRB2</td>
<td>Adapter protein</td>
</tr>
<tr>
<td class="label">Akt1/PKB</td>
<td>Downstream kinase</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/atherosclerosis" style="color:#ef9a9a">Atherosclerosis</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">232 edges</a></td>
</tr>
</table>

Pik3R1 Gene plays an important role in the study of neurodegenerative diseases. This page provides comprehensive information about this topic, including its mechanisms, significance in disease processes, and therapeutic implications.

Pathway Diagram

Introduction

Pik3R1 Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) encodes the p85α regulatory subunit of phosphoinositide 3-kinase (PI3K), a critical signaling molecule that regulates cell survival, growth, and metabolism[@cantley2002][@fruman2017].

Gene Overview

Protein Structure and Function

PIK3R1 encodes the p85α regulatory subunit, which plays essential roles in PI3K/Akt signaling[@cantley2002]:

• Signal transduction: p85α is the main regulatory subunit that links receptor tyrosine kinases to PI3K activation
• Cell survival: PI3K/Akt pathway promotes cell survival and inhibits [apoptosis](/entities/apoptosis)
• Metabolic regulation: Controls glucose uptake, lipid synthesis, and protein synthesis
• Cell growth: Regulates [mTOR](/entities/mtor) signaling and cell cycle progression

Domain Architecture

The p85α protein contains:

• SH3 domain: Proline-rich region for protein-protein interactions
• nSH2 domain: Interacts with phosphorylated tyrosine residues
• iSH2 domain: Mediates dimerization with p110 catalytic subunit
• cSH2 domain: Binds phosphorylated receptors and adaptors

Role in Neurodegeneration

PI3K/Akt Signaling in AD

The PI3K/Akt pathway is critically involved in Alzheimer's disease pathogenesis[@talbot2012][@liu2019]:

PI3K/Akt Signaling in PD

In Parkinson's disease, PI3K/Akt signaling is crucial for[@xing2020][@kim2021]:

• Dopaminergic neuron survival: Akt promotes survival of substantia nigra [neurons](/entities/neurons)
• Mitochondrial function: PI3K/Akt regulates mitochondrial biogenesis and dynamics
• [α-synuclein](/proteins/alpha-synuclein) toxicity: Dysregulated signaling exacerbates α-synuclein aggregation

Insulin Signaling and Neurodegeneration

PI3K is a key mediator of brain insulin signaling[@arnold2018]:

• Type 2 diabetes risk: Insulin resistance increases AD risk through PI3K pathway disruption
• Brain insulin deficiency: AD is increasingly recognized as a "type 3 diabetes" with impaired insulin signaling

Protein Interactions

Expression Pattern

PIK3R1 is expressed throughout the brain:

• Cerebral [cortex](/brain-regions/cortex): High expression in pyramidal neurons
• [Hippocampus](/brain-regions/hippocampus): Particularly in CA1 region
• Cerebellum: Purkinje cells show abundant expression
• Substantia nigra: Dopaminergic neurons

Clinical Significance

Neurodegenerative Disease Associations

• Alzheimer's Disease: Reduced PI3K/Akt signaling; p85α alterations in affected brain regions
• Parkinson's Disease: Impaired PI3K signaling in dopaminergic neurons; association with PINK1/Parkin pathway
• Huntington's Disease: Dysregulated PI3K/Akt/mTOR signaling

Therapeutic Implications

PI3K modulators are being investigated for neurodegenerative diseases[@degroot2023]:

• PI3K activators to enhance neuronal survival
• Selective p85α stabilizers to restore signaling
• Combination therapies targeting multiple nodes of the pathway

Key Publications

See Also

• [PIK3R1 Protein](/proteins/pik3r1-protein)
• [PI3K/Akt Signaling Pathway](/mechanisms/pi3k-akt-signaling)
• [Brain Insulin Signaling](/entities/brain-insulin-signaling)
• [GSK-3β](/entities/gsk3-beta)
• [Amyloid Cascade](/mechanisms/amyloid-cascade)
• [Tau Pathology](/mechanisms/tau-pathology)

Overview

Pik3R1 Gene plays an important role in the study of neurodegenerative diseases. This page provides comprehensive information about this topic, including its mechanisms, significance in disease processes, and therapeutic implications.

Background

The study of Pik3R1 Gene 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.

External Links

• [PubMed](https://pubmed.ncbi.nlm.nih.gov/) - Biomedical literature
• [Alzheimer's Disease Neuroimaging Initiative](https://adni.loni.usc.edu/) - Research data
• [Allen Brain Atlas](https://brain-map.org/) - Brain gene expression data

References

Pathway Diagram

The following diagram shows the key molecular relationships involving PIK3R1 Gene discovered through SciDEX knowledge graph analysis: