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>
{{ 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 ESRRBDisease 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.
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
Mermaid diagram (expand to render)
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 plasticityTherapeutic 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
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 deacetylationGene 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/)