PPARGC1A Gene

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PPARGC1A Gene

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PPARGC1A Gene

Introduction

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">PPARGC1A Gene</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>PPARGC1A</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>PPARG Coactivator 1 Alpha</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>4p15.31</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>10891</td>
</tr>
<tr>
<td class="label">OMIM ID</td>
<td>604517</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000109819</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q9UBX2</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td>Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Type 2 Diabetes, Metabolic Syndrome</td>
</tr>
<tr>
<td class="label">Compound</td>
<td>Status</td>
</tr>
<tr>
<td class="label">AICAR</td>
<td>Research</td>
</tr>
<tr>
<td class="label">Resveratrol</td>
<td>Dietary supplement</td>
</tr>
<tr>
<td class="label">Bezafibrate</td>
<td>FDA approved (lipids)</td>
</tr>
<tr>
<td class="label">Metformin</td>
<td>FDA approved (diabetes)</td>
</tr>
<tr>
<td class="label">Exercise</td>
<td>Clinical</td>
</tr>
</table>

Pathway Diagram

...

PPARGC1A Gene

Introduction

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">PPARGC1A Gene</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>PPARGC1A</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>PPARG Coactivator 1 Alpha</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>4p15.31</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>10891</td>
</tr>
<tr>
<td class="label">OMIM ID</td>
<td>604517</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000109819</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q9UBX2</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td>Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Type 2 Diabetes, Metabolic Syndrome</td>
</tr>
<tr>
<td class="label">Compound</td>
<td>Status</td>
</tr>
<tr>
<td class="label">AICAR</td>
<td>Research</td>
</tr>
<tr>
<td class="label">Resveratrol</td>
<td>Dietary supplement</td>
</tr>
<tr>
<td class="label">Bezafibrate</td>
<td>FDA approved (lipids)</td>
</tr>
<tr>
<td class="label">Metformin</td>
<td>FDA approved (diabetes)</td>
</tr>
<tr>
<td class="label">Exercise</td>
<td>Clinical</td>
</tr>
</table>

Pathway Diagram

Mermaid diagram (expand to render)

Ppargc1A 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.

PPARGC1A (PPARG Coactivator 1 Alpha / PGC-1alpha) is a gene encoding a transcriptional coactivator that regulates mitochondrial biogenesis, energy metabolism, and oxidative stress response. [@stpierre2006]

Overview

Function

PPARGC1A encodes PGC-1α (PPAR gamma coactivator 1-alpha), a transcriptional coactivator that serves as a master regulator of mitochondrial biogenesis and cellular energy metabolism.

Molecular Function

Transcriptional Coactivator: Binds to nuclear receptors and transcription factors to enhance their activity
Mitochondrial Biogenesis: Activates NRF-1, NRF-2, and ERRα to increase mitochondrial DNA replication and protein synthesis
Oxidative Phosphorylation: Upregulates genes involved in the electron transport chain
Fatty Acid Oxidation: Enhances expression of genes for β-oxidation
Gluconeogenesis: Regulates hepatic glucose production
Thermogenesis: Controls brown adipose tissue function

Expression Pattern

PGC-1α is expressed in tissues with high metabolic demand:

Brain: [Neurons](/entities/neurons) (especially in substantia nigra, hippocampus), [astrocytes](/entities/astrocytes)
Skeletal Muscle: High expression in oxidative (slow-twitch) fibers
Heart: Cardiac muscle
Brown Adipose Tissue: Thermogenic adipocytes
Liver: Hepatocytes

In the brain, PGC-1α is particularly important in:

Dopaminergic neurons (high metabolic demand)
Hippocampal neurons (cognitive function)
Cerebellar Purkinje cells

Disease Associations

Alzheimer's Disease

PGC-1α dysfunction contributes to AD:

Reduced PGC-1α in AD brain
Mitochondrial dysfunction and energy deficit
[Aβ](/proteins/amyloid-beta)-induced mitochondrial damage
Therapeutic potential: PGC-1α activators improve cognition in models

Parkinson's Disease

PGC-1α is crucial for dopaminergic neuron survival:

Mitochondrial complex I deficiency in PD
PGC-1α protects against MPTP/6-OHDA toxicity
LRRK2 regulates PGC-1α activity
Gene therapy approaches in development

Huntington's Disease

PGC-1α is downregulated in HD:

Mutant [huntingtin](/proteins/huntingtin-protein) impairs PGC-1α function
Mitochondrial dysfunction in HD
Restoring PGC-1α improves phenotypes in models
Therapeutic target for HD

Metabolic Disorders

Type 2 Diabetes: PGC-1α variants associated with insulin resistance
Obesity: Reduced PGC-1α in adipose tissue
Metabolic Syndrome: Therapeutic target

Therapeutic Targeting

PGC-1α Activators

Gene Therapy

AAV-PPARGC1A for neurodegenerative diseases
SIRT1 activators to enhance PGC-1α activity

Key Publications

[Wareski P et al. (2009) PGC-1alpha and PGC-1beta regulate mitochondrial density in neurons. J Biol Chem. PMID:19211836](https://pubmed.ncbi.nlm.nih.gov/19211836)

[St-Pierre J et al. (2006) Suppression of reactive oxygen species and neurodegeneration by the PGC-1 transcriptional coactivators. Cell. PMID:16547501](https://pubmed.ncbi.nlm.nih.gov/16547501)

[Cui L et al. (2006) Transcriptional activation of human PGC-1alpha by Huntington disease protein. Cell. PMID:16547502](https://pubmed.ncbi.nlm.nih.gov/16547502)

External Links

[NCBI Gene: PPARGC1A](https://www.ncbi.nlm.nih.gov/gene/10891)
[UniProt: Q9UBX2](https://www.uniprot.org/uniprot/Q9UBX2)
[OMIM: 604517](https://www.omim.org/entry/604517)
[Ensembl: ENSG00000109819](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000109819)

Background

The study of Ppargc1A 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.

Allen Brain Atlas Resources

Allen Human Brain Atlas: [PPARGC1A gene expression](https://human.brain-map.org/microarray/search/show?search_term=PPARGC1A)
Allen Mouse Brain Atlas: [PPARGC1A expression](https://mouse.brain-map.org/search/index.html?query=PPARGC1A)
Allen Cell Type Atlas: [Transcriptomic cell type reference](https://portal.brain-map.org/atlases-and-data/rnaseq)
BrainSpan Atlas: [PPARGC1A developmental expression](https://www.brainspan.org/rnaseq/search/index.html?search_term=PPARGC1A)

References

[Wareski P, et al, PGC-1alpha and PGC-1beta regulate mitochondrial density in neurons (2009)](https://pubmed.ncbi.nlm.nih.gov/19211836/)

[St-Pierre J, et al, Suppression of reactive oxygen species and neurodegeneration by the PGC-1 transcriptional coactivators (2006)](https://pubmed.ncbi.nlm.nih.gov/16547501/)

[Cui L, et al, Transcriptional activation of human PGC-1alpha by Huntington disease protein (2006)](https://pubmed.ncbi.nlm.nih.gov/16547502/)

[Handschin C, Spiegelman BM, Peroxisome proliferator-activated receptor gamma coactivator 1 coactivators, energy metabolism, and metabolic diseases (2007)](https://pubmed.ncbi.nlm.nih.gov/17499144/)

[Lin J, et al, Transcriptional co-activator PGC-1 alpha drives the formation of slow-twitch muscle fibres (2002)](https://pubmed.ncbi.nlm.nih.gov/12181572/)

From the [SciDEX Exchange](/exchange) — scored by multi-agent debate

[Digital Twin-Guided Metabolic Reprogramming](/hypothesis/h-b0cda336) — <span style="color:#81c784;font-weight:600">0.60</span> · Target: PPARGC1A/PRKAA1
[Perforant Path Presynaptic Terminal Protection Strategy](/hypothesis/h-76888762) — <span style="color:#ffd54f;font-weight:600">0.48</span> · Target: PPARGC1A

Pathway Diagram

The following diagram shows the key molecular relationships involving PPARGC1A Gene discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

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Related Entities

PPARGC1A

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kg_node_id	PPARGC1A
entity_type	gene
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-da518be74d31
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'genes-ppargc1a'}
_schema_version	1

📊 Evidence Profile Foundational

Evidence Balance

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Certainty

100%

Debates

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Incoming

149

Outgoing

91

0 supporting 0 contradicting 0 neutral

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📗 Cite This Artifact

PPARGC1A Gene

PPARGC1A Gene

Introduction

Pathway Diagram

PPARGC1A Gene

Introduction

Pathway Diagram

Overview

Function

Molecular Function

Expression Pattern

Disease Associations

Alzheimer's Disease

Parkinson's Disease

Huntington's Disease

Metabolic Disorders

Therapeutic Targeting

PGC-1α Activators

Gene Therapy

Key Publications

See Also

External Links

Background

Allen Brain Atlas Resources

References

Pathway Diagram

💬 Discussion

📗 Cite This Artifact

PPARGC1A Gene

PPARGC1A Gene

Introduction

Pathway Diagram

PPARGC1A Gene

Introduction

Pathway Diagram

Overview

Function

Molecular Function

Expression Pattern

Disease Associations

Alzheimer's Disease

Parkinson's Disease

Huntington's Disease

Metabolic Disorders

Therapeutic Targeting

PGC-1α Activators

Gene Therapy

Key Publications

See Also

External Links

Background

Allen Brain Atlas Resources

References

Related Hypotheses

Pathway Diagram

💬 Discussion