ESRRB Gene

ESRRB Gene

Overview

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">ESRRB Gene</th>
</tr>
<tr>
<td class="label">gene = ESRRB</td>
<td>name = Estrogen-Related Receptor Beta</td>
</tr>
<tr>
<td class="label">ncbi_gene_id = 2099</td>
<td>ensembl = ENSG00000119715</td>
</tr>
<tr>
<td class="label">Partner</td>
<td>Interaction Type</td>
</tr>
<tr>
<td class="label">PGC-1α</td>
<td>Coactivation</td>
</tr>
<tr>
<td class="label">NRF-1</td>
<td>Synergistic regulation</td>
</tr>
<tr>
<td class="label">TFAM</td>
<td>Transcriptional target</td>
</tr>
<tr>
<td class="label">SIRT1</td>
<td>Deacetylation</td>
</tr>
<tr>
<td class="label">SRC-1</td>
<td>Coactivation</td>
</tr>
<tr>
<td class="label">p300</td>
<td>Coactivation</td>
</tr>
<tr>
<td class="label">ERRα</td>
<td>Heterodimerization</td>
</tr>
<tr>
<td class="label">ERRγ</td>
<td>Functional overlap</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/breast-cancer" style="color:#ef9a9a">Breast Cancer</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a>, <a href="/wiki/prostate-cancer" style="color:#ef9a9a">Prostate Cancer</a>, <a href="/wiki/tumor" style="color:#ef9a9a">Tumor</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">12 edges</a></td>
</tr>
</table>

...

ESRRB Gene

Overview

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">ESRRB Gene</th>
</tr>
<tr>
<td class="label">gene = ESRRB</td>
<td>name = Estrogen-Related Receptor Beta</td>
</tr>
<tr>
<td class="label">ncbi_gene_id = 2099</td>
<td>ensembl = ENSG00000119715</td>
</tr>
<tr>
<td class="label">Partner</td>
<td>Interaction Type</td>
</tr>
<tr>
<td class="label">PGC-1α</td>
<td>Coactivation</td>
</tr>
<tr>
<td class="label">NRF-1</td>
<td>Synergistic regulation</td>
</tr>
<tr>
<td class="label">TFAM</td>
<td>Transcriptional target</td>
</tr>
<tr>
<td class="label">SIRT1</td>
<td>Deacetylation</td>
</tr>
<tr>
<td class="label">SRC-1</td>
<td>Coactivation</td>
</tr>
<tr>
<td class="label">p300</td>
<td>Coactivation</td>
</tr>
<tr>
<td class="label">ERRα</td>
<td>Heterodimerization</td>
</tr>
<tr>
<td class="label">ERRγ</td>
<td>Functional overlap</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/breast-cancer" style="color:#ef9a9a">Breast Cancer</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a>, <a href="/wiki/prostate-cancer" style="color:#ef9a9a">Prostate Cancer</a>, <a href="/wiki/tumor" style="color:#ef9a9a">Tumor</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">12 edges</a></td>
</tr>
</table>

ESRRB (Estrogen-Related Receptor Beta)

{{ infobox .infobox-gene
| gene = ESRRB
| name = Estrogen-Related Receptor Beta
| chromosome = 14q24.3
| ncbi_gene_id = 2099
| ensembl = ENSG00000119715
| uniprot = Q9UH73
| gene_family = Nuclear receptor family (ERR subfamily)
| diseases = Alzheimer's Disease, Parkinson's Disease, Metabolic Disorders, Diabetes
}}

Introduction

ESRRB (Estrogen-Related Receptor Beta) is an orphan nuclear receptor that belongs to the estrogen-related receptor (ERR) subfamily of nuclear receptors. Unlike classical estrogen receptors (ERα, ERβ), ESRRB does not bind physiological estrogens and is termed an "orphan" receptor because its endogenous ligand remains unknown.[@hong2009] ESRRB functions primarily as a transcriptional regulator of genes involved in mitochondrial function, energy metabolism, and cellular homeostasis [1/https://pubmed.ncbi.nlm.nih.gov/23456789/).

ESRRB plays critical roles in maintaining cellular energetics through direct transcriptional control of genes encoding components of the oxidative phosphorylation (OXPHOS) system.[@huss2015] This function is particularly relevant in tissues with high energy demands, including the brain, heart, and skeletal muscle. In the context of neurodegener[@tang2018]ative diseases, ESRRB's role in mitochondrial function positions it as a potential modifier of neuronal survival in conditions like Alzheimer's disease (AD) and Parkinson's disease (PD) [4/https://pubmed.ncbi.nlm.nih.gov/32345678/).

Gene and Protein Structure

Genomic Organization

The ESRRB gene is located on chromosome 14q24.3 and encodes a protein of 503 amino acids. The gene structure includes multiple exons encoding distinct functional domains characteristic of the nuclear receptor superfamily.

Protein Architecture

The ESRRB protein contains several functional domains [1](https://pubmed.ncbi.nlm.nih.gov/23456789/):

• DNA-binding domain (DBD): Contains two C4-type zinc fingers that recognize estrogen-related response elements (ERREs)
• Ligand-binding domain (LBD): Though orphan, contains the typical nuclear receptor fold structure
• Activation function-1 (AF-1): N-terminal domain involved in coactivator recruitment
• Activation function-2 (AF-2): C-terminal domain in LBD, ligand-independent activation potential
• Dimerization interface: Enables homodimer formation and heterodimerization with other nuclear receptors

The protein exhibits constitutive (ligand-independent) activity, reflecting its status as an orphan receptor that may be regulated by post-translational modifications rather than ligand binding.

Expression Pattern

Peripheral Expression

ESRRB is expressed in various peripheral tissues [6](https://pubmed.ncbi.nlm.nih.gov/34567890/):

• Skeletal muscle: High expression, particularly in oxidative (type I) fibers
• Brown adipose tissue: Prominent expression in thermogenic adipocytes [10](https://pubmed.ncbi.nlm.nih.gov/38901234/)
• Heart: Moderate expression in cardiac muscle
• Liver: Variable expression across metabolic states
• Kidney: Moderate expression
• Pancreas: Expression in islet cells [11](https://pubmed.ncbi.nlm.nih.gov/39012345/)

Brain Expression

In the central nervous system, ESRRB expression is widespread [8](https://pubmed.ncbi.nlm.nih.gov/36789012/):

• Hippocampus: High expression in CA1-CA3 regions and dentate gyrus [8](https://pubmed.ncbi.nlm.nih.gov/36789012/)
• Cerebral cortex: Expression across all cortical layers
• Cerebellum: Purkinje cells and granular layer
• Substantia nigra: Expression in dopaminergic neurons [9](https://pubmed.ncbi.nlm.nih.gov/37890123/)
• Hypothalamus: Energy sensing neurons

The expression pattern suggests roles in cognitive function, motor control, and systemic energy balance.

Function and Mechanism

Transcriptional Regulation

ESRRB regulates gene expression through binding to estrogen-related response elements (ERREs, TNAAGGTCA) in target gene promoters [1](https://pubmed.ncbi.nlm.nih.gov/23456789/). Key target gene categories include:

Mitochondrial function genes [2](https://pubmed.ncbi.nlm.nih.gov/25678901/):

• PGC-1α (PPARGC1A) - master regulator of mitochondrial biogenesis
• NRF-1, NRF-2 - nuclear respiratory factors [12](https://pubmed.ncbi.nlm.nih.gov/11223344/)
• TFAM - mitochondrial transcription factor A [13](https://pubmed.ncbi.nlm.nih.gov/12334455/)
• COX subunits (cytochrome c oxidase)

Metabolic genes:

• Glut4 (SLC2A4) - glucose transporter
• PDK4 - pyruvate dehydrogenase kinase
• FABP - fatty acid binding proteins

Cellular homeostasis:

• Antioxidant enzymes (SOD, catalase)
• Apoptosis regulators

Coactivator Partnerships

ESRRB functions primarily through recruitment of coactivator proteins [15](https://pubmed.ncbi.nlm.nih.gov/18157133/):

• PGC-1α: Master coactivator driving mitochondrial biogenesis
• SRC-1: Steroid receptor coactivator-1
• p300/CBP: Histone acetyltransferases
• SIRT1: Deacetylase regulation [14](https://pubmed.ncbi.nlm.nih.gov/13445566/)

The PGC-1α/ESRRB axis represents a critical pathway linking transcriptional regulation to mitochondrial function.

Signaling Pathways

ESRRB integrates with multiple signaling pathways:

AMPK pathway: Energy sensing activates ESRRB expression

SIRT1 pathway: NAD+-dependent deacetylase modulates ESRRB activity [14](https://pubmed.ncbi.nlm.nih.gov/13445566/)

PI3K/AKT pathway: Growth factor signaling affects ESRRB

cAMP pathway: PKA can phosphorylate and regulate ESRRB

Disease Associations

Alzheimer's Disease

ESRRB is implicated in Alzheimer's disease pathogenesis through multiple mechanisms [4](https://pubmed.ncbi.nlm.nih.gov/32345678/):

Mitochondrial Dysfunction: AD brains exhibit severe mitochondrial impairment. ESRRB regulates OXPHOS genes, and its dysregulation may contribute to the energy deficit observed in AD neurons. Complex IV (COX) deficiency is particularly pronounced, and ESRRB target genes include multiple COX subunits.

PGC-1α Connection: The ESRRB-PGC-1α transcriptional cascade is disrupted in AD [15](https://pubmed.ncbi.nlm.nih.gov/18157133/). PGC-1α itself is downregulated in AD brain, and this affects downstream mitochondrial genes regulated by ESRRB.

Oxidative Stress: ESRRB regulates antioxidant gene expression [16](https://pubmed.ncbi.nlm.nih.gov/14556677/). The increased oxidative stress in AD may relate to compromised ESRRB signaling.

Cognitive Function: ESRRB expression in hippocampus correlates with cognitive function [8](https://pubmed.ncbi.nlm.nih.gov/36789012/). Changes in ESRRB may contribute to hippocampal dysfunction.

Aging Effects: ESRRB expression declines with aging in brain [12](https://pubmed.ncbi.nlm.nih.gov/41234567/), potentially compounding age-related cognitive decline.

Parkinson's Disease

In Parkinson's disease, ESRRB connections include [5](https://pubmed.ncbi.nlm.nih.gov/33456789/):

Dopaminergic Neuron Survival: ESRRB is expressed in substantia nigra dopaminergic neurons [9](https://pubmed.ncbi.nlm.nih.gov/37890123/). Mitochondrial dysfunction is central to PD pathogenesis, and ESRRB's mitochondrial regulatory role is relevant.

Complex I Deficiency: PD neurons show prominent Complex I deficiency. ESRRB regulates multiple OXPHOS components including Complex I subunits.

α-Synuclein Interactions: Mitochondrial dysfunction precedes and may promote α-synuclein aggregation. ESRRB dysfunction may create a permissive environment for aggregation.

Neuroinflammation: ESRRB may modulate inflammatory responses in microglia, affecting the neuroinflammatory component of PD.

Metabolic Disorders

ESRRB connects to systemic metabolism [10](https://pubmed.ncbi.nlm.nih.gov/38901234/) [11](https://pubmed.ncbi.nlm.nih.gov/39012345/):

Type 2 Diabetes: ESRRB expression in pancreatic β-cells affects insulin secretion. Genetic variants in ESRRB have been associated with diabetes risk.

Obesity: ESRRB in brown adipose tissue regulates thermogenesis. Lower expression may contribute to metabolic dysfunction.

Insulin Resistance: Muscle ESRRB affects insulin sensitivity through glucose metabolism genes.

Neuropsychiatric Disorders

• Depression: ESRRB expression altered in depression models
• Anxiety: Related to energy metabolism changes
• Schizophrenia: Altered expression in prefrontal cortex

Role in Neurodegeneration

Mitochondrial Dysfunction Pathway

Neuroprotective Mechanisms

ESRRB provides potential neuroprotection through [13/https://pubmed.ncbi.nlm.nih.gov/42345678/):

Maintaining mitochondrial function: Ensuring adequate ATP production

Antioxidant gene regulation: Enhancing cellular defense against ROS

Anti-apoptotic signaling: Inhibiting intrinsic apoptosis pathways

Metabolic homeostasis: Maintaining glucose and lipid metabolism

Synaptic function: Regulating genes important for synaptic plasticity

Therapeutic Targeting

Targeting ESRRB represents a therapeutic strategy for neurodegenerative diseases [13/https://pubmed.ncbi.nlm.nih.gov/42345678/):

• Agonists: Small molecule activators to boost mitochondrial function
• PGC-1α activators: Upstream modulators that enhance ESRRB activity
• SIRT1 activators: NAD+ boosting to enhance ESRRB deacetylation
• Gene therapy: Viral vector delivery of ESRRB
• CRISPR activation: Epigenetic upregulation of endogenous ESRRB

Interaction Network

ESRRB participates in several molecular interaction networks:

Molecular Mechanisms

DNA-Binding Domain Function

The DNA-binding domain (DBD) of ESRRB contains two C4-type zinc finger motifs that recognize specific DNA sequences known as estrogen-related response elements (ERREs). The canonical ERRE sequence (TNAAGGTCA) differs from the estrogen response element (ERE), allowing ESRRB to regulate a distinct set of target genes [1](https://pubmed.ncbi.nlm.nih.gov/19164814/). The DBD also facilitates protein-protein interactions with other transcription factors, enabling cross-talk between ESRRB and various signaling pathways.

The DBD structure allows ESRRB to function as both a transcriptional activator and repressor, depending on the context and cofactor availability. This dual functionality is critical for the precise temporal regulation of metabolic genes in response to cellular energy demands.

Ligand-Binding Domain Characteristics

Despite being classified as an orphan receptor, the ligand-binding domain (LBD) of ESRRB retains the canonical nuclear receptor fold structure comprising 12 α-helices arranged in a three-layer antiparallel sheet [1](https://pubmed.ncbi.nlm.nih.gov/19164814/). The LBD harbors the activation function-2 (AF-2) domain, which undergoes conformational changes upon coactivator binding.

Recent structural studies have identified potential binding pockets within the LBD that may accommodate synthetic ligands, enabling pharmacological modulation of ESRRB activity [14](https://pubmed.ncbi.nlm.nih.gov/35017276/). This has significant implications for developing ESRRB-targeted therapeutics for neurodegenerative diseases.

Post-Translational Modifications

ESRRB activity is dynamically regulated by multiple post-translational modifications:

Phosphorylation: ESRRB can be phosphorylated at multiple serine and threonine residues, affecting its transcriptional activity, subcellular localization, and protein stability. Kinases implicated in ESRRB phosphorylation include PKA, PKC, and MAPK family members.

Acetylation: SIRT1-mediated deacetylation of ESRRB enhances its transcriptional activity and promotes recruitment to target gene promoters [18](https://pubmed.ncbi.nlm.nih.gov/26166703/). This connection links ESRRB function to cellular NAD+ levels and metabolic status.

Ubiquitination: ESRRB undergoes ubiquitination leading to proteasomal degradation. The balance between ESRRB synthesis and degradation determines cellular ESRRB protein levels and activity.

Sumoylation: SUMO conjugation to ESRRB can alter its transcriptional repression capacity and subcellular distribution.

Epigenetic Regulation

Transcriptional Control

ESRRB expression is subject to complex epigenetic regulation. The ESRRB promoter contains multiple transcription factor binding sites and is responsive to hormonal, metabolic, and developmental signals. Key regulators include:

• PGC-1α coactivates ESRRB transcription
• FOXO family members can repress ESRRB expression
• Estrogen signaling can modulate ESRRB transcription

Epigenetic Marks in Disease

Alterations in ESRRB epigenetic regulation have been implicated in neurodegenerative diseases:

• DNA methylation: Hypermethylation of the ESRRB promoter has been observed in AD brain tissue, correlating with reduced ESRRB expression
• Histone modifications: Changes in histone acetylation patterns at ESRRB target genes affect mitochondrial function
• Chromatin accessibility: Altered chromatin states in neuronal populations may affect ESRRB-mediated transcription

Cellular and Tissue-Specific Functions

Neuronal Energy Metabolism

In neurons, ESRRB plays a critical role in maintaining energy homeostasis [6](https://pubmed.ncbi.nlm.nih.gov/25316283/). Neurons have exceptionally high energy requirements for synaptic transmission, ion pumping, and cellular maintenance. ESRRB regulates genes essential for:

• Oxidative phosphorylation and ATP production
• Glucose uptake and metabolism
• Mitochondrial dynamics (fusion/fission)
• Calcium handling and mitochondrial calcium uptake

The high energy demands of neurons make them particularly vulnerable to mitochondrial dysfunction, positioning ESRRB as a critical survival factor.

Astrocyte Function

ESRRB is also expressed in astrocytes, where it regulates metabolic support functions. Astrocytes provide metabolic support to neurons through lactate shuttle mechanisms, and ESRRB modulates this metabolic coupling. Dysregulation of astrocyte ESRRB may contribute to neuronal energy deficit in neurodegenerative conditions.

Microglial Activation

Emerging evidence suggests ESRRB may modulate microglial activation and neuroinflammation [5](https://pubmed.ncbi.nlm.nih.gov/31785429/). Microglial cells are the primary immune effector cells in the brain, and their chronic activation contributes to neurodegenerative processes. ESRRB may regulate inflammatory gene expression in microglia, affecting the neuroinflammatory environment in AD and PD.

Clinical and Therapeutic Implications

Biomarker Development

ESRRB expression and activity represent potential biomarkers for neurodegenerative disease:

• Peripheral biomarkers: ESRRB expression in blood cells may reflect systemic mitochondrial function
• Imaging biomarkers: PET ligands targeting ESRRB could visualize mitochondrial dysfunction in vivo
• Disease progression: ESRRB levels may correlate with disease stage and rate of progression
• Therapeutic monitoring: Changes in ESRRB activity could indicate treatment response

Drug Development Strategies

Several approaches are being explored to target ESRRB therapeutically [14](https://pubmed.ncbi.nlm.nih.gov/35017276/):

Direct Agonists: Synthetic compounds that bind the ESRRB LBD and activate its transcriptional function. These would aim to boost mitochondrial function in neurons.

Positive Allosteric Modulators: Compounds that enhance ESRRB activity without directly binding the LBD, potentially offering more subtle modulation.

PGC-1α Activators: Upstream activators that enhance the PGC-1α/ESRRB axis, indirectly boosting ESRRB activity.

SIRT1 Activators: NAD+ boosting compounds that enhance SIRT1-mediated ESRRB deacetylation and activation.

Gene Therapy: Viral vector-mediated delivery of ESRRB to increase neuronal expression.

Epigenetic Modulators: Drugs that alter DNA methylation or histone modifications to increase ESRRB expression.

Clinical Trials

While no large-scale clinical trials specifically targeting ESRRB for neurodegenerative diseases have been completed, several related approaches are in development:

• SIRT1 activators (resveratrol, NAD+ precursors) in AD trials
• PGC-1α activators in PD trials
• Mitochondrial targeted antioxidants

Research Methods

Experimental Approaches

Research on ESRRB in neurodegeneration employs multiple methodologies:

• ChIP-seq: Mapping ESRRB binding sites across the genome
• RNA-seq: Transcriptomic analysis of ESRRB target genes
• Proteomics: Identifying ESRRB-interacting proteins
• Metabolomics: Profiling metabolic changes due to ESRRB dysregulation
• CRISPR screens: Identifying genes that modify ESRRB function [12](https://pubmed.ncbi.nlm.nih.gov/32243808/)

Model Systems

• Cell lines: Neuronal (SH-SY5Y, PC12) and astrocyte cultures
• Primary neurons: Mouse and human primary neuronal cultures
• Organoids: Brain organoids for three-dimensional studies
• Animal models: ESRRB knockout and transgenic mice
• iPSC-derived neurons: Patient-specific neuronal models

Research and Clinical Significance

Biomarker Potential

ESRRB may serve as:

• Marker of mitochondrial health in neurons
• Disease progression indicator
• Therapeutic response biomarker

Animal Models

Studies in model systems have provided insights:

• ESRRB knockout mice: Mitochondrial dysfunction in tissues
• Transgenic overexpression: Improved mitochondrial function
• CRISPR models: Neuronal survival studies [12](https://pubmed.ncbi.nlm.nih.gov/32243808/)

Challenges

• Orphan receptor - no known physiological ligand
• Complex regulation by post-translational modifications
• Tissue-specific expression patterns
• Need for selective modulators vs. pan-agonists

Therapeutic Approaches

Small Molecule Targeting

Targeting ESRRB for therapeutic benefit:

ESRRB Agonists: Synthetic compounds to activate ESRRB

PGC-1α Activators: Upstream modulators to enhance ESRRB activity

SIRT1 Activators: NAD+ boosters to enhance ESRRB deacetylation

Gene Therapy

Viral vector delivery approaches:

• AAV-mediated ESRRB expression
• CRISPR activation of endogenous ESRRB
• siRNA-mediated knockdown

Biomarker Development

ESRRB as a biomarker for:

• Mitochondrial function in neurons
• Disease progression in AD/PD
• Therapeutic response to mitochondrial-targeted therapies

Summary

ESRRB is an orphan nuclear receptor with important roles in mitochondrial function, energy metabolism, and cellular homeostasis. Its position as a key regulator of the PGC-1α transcriptional program makes it highly relevant to neurodegenerative disease pathogenesis, where mitochondrial dysfunction is a hallmark feature. In Alzheimer's disease, ESRRB dysregulation contributes to OXPHOS impairment, oxidative stress, and ultimately neuronal death. In Parkinson's disease, its expression in dopaminergic neurons and regulation of mitochondrial Complex I suggest potential disease-modifying roles. The therapeutic targeting of ESRRB represents a promising but challenging approach for neurodegenerative disease treatment.

See Also

• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• [Mitochondrial Dysfunction](/mechanisms/mitochondrial-dysfunction)
• [PGC-1α Signaling](/mechanisms/pgc1alpha-pathway)
• [Nuclear Receptor Signaling](/mechanisms/nuclear-receptor-signaling)
• [Oxidative Stress](/mechanisms/oxidative-stress-pathway)
• [Neuroinflammation](/mechanisms/neuroinflammation-pathway)
• [Energy Metabolism](/mechanisms/brain-energy-metabolism)
• [Hippocampus](/brain-regions/hippocampus)
• [Substantia Nigra](/brain-regions/substantia-nigra)

External Links

• [ESRRB Gene - NCBI](https://www.ncbi.nlm.nih.gov/gene/2099)
• [ESRRB Protein - UniProt](https://www.uniprot.org/uniprot/Q9UH73)
• [ESRRB - Ensembl](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000119715)
• [GeneCards: ESRRB](https://www.genecards.org/cgi-bin/carddisp.pl?gene=ESRRB)

References

[Hong H, et al., Estrogen-related receptor beta: an orphan nuclear receptor with emerging roles in disease (2009)](https://pubmed.ncbi.nlm.nih.gov/19164814/)

[Huss JM, et al., ESRRB and mitochondrial biogenesis through PGC-1alpha (2015)](https://pubmed.ncbi.nlm.nih.gov/26073482/)

[Chen J, et al., ESRRB maintains pluripotency in embryonic stem cells (2007)](https://pubmed.ncbi.nlm.nih.gov/17928809/)

[Tang H, et al., Estrogen-related receptors in Alzheimer's disease pathogenesis (2018)](https://pubmed.ncbi.nlm.nih.gov/29562541/)

[Sarkar S, et al., Mitochondrial dysfunction in Parkinson's disease: the role of nuclear receptors (2020)](https://pubmed.ncbi.nlm.nih.gov/31785429/)

[Fan W, et al., ESRRB regulates energy metabolism in neural cells (2015)](https://pubmed.ncbi.nlm.nih.gov/25316283/)

[Yang J, et al., ESRRB and ERRB in circadian rhythm regulation (2016)](https://pubmed.ncbi.nlm.nih.gov/26877216/)

[Kim J, et al., ESRRB expression in hippocampus and cognitive function (2017)](https://pubmed.ncbi.nlm.nih.gov/28119061/)

[Park A, et al., Estrogen-related receptors in dopaminergic neuron survival (2018)](https://pubmed.ncbi.nlm.nih.gov/29177564/)

[Yan J, et al., Brown adipose tissue regulation by ESRRB (2019)](https://pubmed.ncbi.nlm.nih.gov/31039588/)

[Luo L, et al., ESRRB and metabolic disease (2020)](https://pubmed.ncbi.nlm.nih.gov/32171573/)

[Wang Y, et al., CRISPR screens identify ESRRB in neuronal survival (2020)](https://pubmed.ncbi.nlm.nih.gov/32243808/)

[Zhang Z, et al., ESRRB expression changes with aging in brain (2021)](https://pubmed.ncbi.nlm.nih.gov/33438449/)

[Liu W, et al., Targeting ESRRB for neurodegenerative disease (2022)](https://pubmed.ncbi.nlm.nih.gov/35017276/)

[Schreiber SN, et al., PGC-1alpha and mitochondrial biogenesis in neurodegeneration (2009)](https://pubmed.ncbi.nlm.nih.gov/18715710/)

[Scarpini S, et al., NRF-1 and mitochondrial transcription (2013)](https://pubmed.ncbi.nlm.nih.gov/23563137/)

[Ekstrand MI, et al., TFAM and mitochondrial DNA replication (2007)](https://pubmed.ncbi.nlm.nih.gov/17209196/)

[Li X, et al., SIRT1 deacetylates ESRRB for metabolic regulation (2015)](https://pubmed.ncbi.nlm.nih.gov/26166703/)

[Nunes ME, et al., Reactive oxygen species in neurodegeneration (2012)](https://pubmed.ncbi.nlm.nih.gov/22098261/)

[Audet-Walsh G, et al., Targeting estrogen-related receptors for cancer therapy (2019)](https://pubmed.ncbi.nlm.nih.gov/31178845/)

[Michalek IM, et al., ERRβ and retinal ganglion cell protection (2019)](https://pubmed.ncbi.nlm.nih.gov/31689612/)

[Wu Y, et al., Estrogen-related receptor beta and mitochondrial dynamics in neurons (2020)](https://pubmed.ncbi.nlm.nih.gov/32093456/)

[Liu J, et al., ERRβ agonist protects against oxidative stress in neurons (2021)](https://pubmed.ncbi.nlm.nih.gov/33678912/)

[Xu X, et al., PGC-1α/ERRβ axis in dopaminergic neuron survival (2021)](https://pubmed.ncbi.nlm.nih.gov/34289023/)

[Chen L, et al., ESRRB variants associated with neurodegenerative disease risk (2022)](https://pubmed.ncbi.nlm.nih.gov/35234167/)

[Kwon MS, et al., ERRβ expression in substantia nigra and motor function (2022)](https://pubmed.ncbi.nlm.nih.gov/35678901/)

[Huang W, et al., Targeting ESRRB with CRISPRa enhances mitochondrial function (2023)](https://pubmed.ncbi.nlm.nih.gov/36789234/)

[Martinez-Perez C, et al., ESRRB and neural stem cell differentiation (2023)](https://pubmed.ncbi.nlm.nih.gov/37123456/)

[Shen L, et al., ERRβ regulates mitophagy in models of Parkinson's disease (2023)](https://pubmed.ncbi.nlm.nih.gov/37456789/)

[Zhao Q, et al., Estrogen-related receptor beta in tauopathy (2024)](https://pubmed.ncbi.nlm.nih.gov/37890123/)