TAZ (WWTR1)

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TAZ (WWTR1)

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TAZ (WWTR1)

<div class="infobox infobox-gene">
<table>
<tr><th colspan="2" style="background:#e8f4ea;">TAZ (WWTR1)</th></tr>
<tr><td><b>Gene Symbol</b></td><td>TAZ / WWTR1</td></tr>
<tr><td><b>Full Name</b></td><td>WW Domain Containing Transcription Regulator 1</td></tr>
<tr><td><b>Chromosomal Location</b></td><td>3q24</td></tr>
<tr><td><b>NCBI Gene ID</b></td><td>[25937](https://www.ncbi.nlm.nih.gov/gene/25937)</td></tr>
<tr><td><b>UniProt ID</b></td><td>[Q9GZV0](https://www.uniprot.org/uniprot/Q9GZV0)</td></tr>
<tr><td><b>Ensembl ID</b></td><td>ENSG00000118445</td></tr>
<tr><td><b>Associated Diseases</b></td><td>[Alzheimer's Disease](/diseases/alzheimers-disease), [Parkinson's Disease](/diseases/parkinsons-disease), cancer, pulmonary fibrosis</td></tr>
</table>
</div>

Pathway Diagram

...

TAZ (WWTR1)

<div class="infobox infobox-gene">
<table>
<tr><th colspan="2" style="background:#e8f4ea;">TAZ (WWTR1)</th></tr>
<tr><td><b>Gene Symbol</b></td><td>TAZ / WWTR1</td></tr>
<tr><td><b>Full Name</b></td><td>WW Domain Containing Transcription Regulator 1</td></tr>
<tr><td><b>Chromosomal Location</b></td><td>3q24</td></tr>
<tr><td><b>NCBI Gene ID</b></td><td>[25937](https://www.ncbi.nlm.nih.gov/gene/25937)</td></tr>
<tr><td><b>UniProt ID</b></td><td>[Q9GZV0](https://www.uniprot.org/uniprot/Q9GZV0)</td></tr>
<tr><td><b>Ensembl ID</b></td><td>ENSG00000118445</td></tr>
<tr><td><b>Associated Diseases</b></td><td>[Alzheimer's Disease](/diseases/alzheimers-disease), [Parkinson's Disease](/diseases/parkinsons-disease), cancer, pulmonary fibrosis</td></tr>
</table>
</div>

Pathway Diagram

Mermaid diagram (expand to render)

Overview

TAZ (Transcriptional coactivator with PDZ-binding motif), also known as WWTR1, is a key transcriptional co-activator in the [Hippo signaling pathway](/mechanisms/hippo-signaling-pathway). TAZ functions by interacting with transcription factors, particularly TEAD family proteins, to regulate gene expression programs involved in cell proliferation, stem cell maintenance, tissue homeostasis, and cellular response to mechanical cues. Unlike its paralog [YAP](/genes/yap1), TAZ lacks a canonical transactivation domain and primarily exerts its effects through TEAD-mediated transcription[@wang2009].

TAZ has emerged as a significant player in neurodegenerative disease pathogenesis, with growing evidence implicating this Hippo pathway effector in both [Alzheimer's Disease](/diseases/alzheimers-disease) and [Parkinson's Disease](/diseases/parkinsons-disease). The protein regulates critical cellular processes including mitochondrial function, neuroinflammation, synaptic plasticity, and neuronal survival—all of which are perturbed in neurodegenerative conditions[@liu2022].

Gene and Protein Structure

Structural Features

The TAZ protein (WWTR1) contains several functional domains that mediate its protein-protein interactions and transcriptional activity:

WW Domain: Located at the N-terminus, this conserved domain mediates interactions with proline-rich motifs in target proteins. The WW domain is essential for TAZ's ability to bind to transcription factors and signaling molecules[@wang2009].

TEAD-binding Domain: TAZ interacts with TEAD transcription factors through a specific binding interface. This interaction is crucial for TAZ's transcriptional co-activator function and is a major focus of therapeutic development[@pobbati2023].

PDZ-binding Motif: Located at the C-terminus, this motif allows TAZ to bind to PDZ domain-containing proteins, facilitating its localization to specific cellular compartments and protein complexes.

Transactivation Domain: While TAZ lacks the strong transactivation domain present in YAP, it possesses regulatory regions that contribute to transcriptional activation through partnership with other co-activators.

Isoforms and Variants

Multiple TAZ isoforms have been described, including:

isoform 1: Full-length protein (400 amino acids)
Shorter isoforms: Generated through alternative splicing, these may have distinct functional properties

Polymorphisms in the WWTR1 gene have been associated with altered risk for certain neurodegenerative conditions in genome-wide association studies, though functional validation remains ongoing.

Molecular Mechanisms

Hippo Pathway Integration

TAZ serves as a downstream effector of the [Hippo signaling pathway](/mechanisms/hippo-pathway-neurodegeneration), a highly conserved pathway that controls organ size by regulating cell proliferation, apoptosis, and stem cell function. The core Hippo kinase cascade includes MST1/2, LATS1/2, and SAV1, which phosphorylate and inhibit YAP/TAZ under normal conditions[@hong2019].

Key regulatory mechanisms include:

Phosphorylation-dependent inhibition: LATS1/2-mediated phosphorylation creates binding sites for 14-3-3 proteins, sequestering TAZ in the cytoplasm
Proteasomal degradation: Sustained phosphorylation leads to β-TrCP-mediated ubiquitination and degradation
Alternative splicing: The microprocessor complex regulates TAZ isoform expression in response to cell density[@mori2014]

Transcriptional Targets

TAZ regulates numerous target genes through its interaction with TEAD and other transcription factors:

| Target Category | Examples | Function |
|-----------------|----------|----------|
| Proliferation | CTGF, CYR61 | Cell cycle regulation |
| Mitochondrial | PGC-1α, TFAM | Mitochondrial biogenesis |
| Synaptic | PSD95, Synapsin | Synaptic function |
| Inflammatory | IL-6, TNF-α | Neuroinflammation modulation |

Role in Alzheimer's Disease

Amyloid-Beta Metabolism

TAZ has been shown to modulate [amyloid-beta](/proteins/amyloid-beta) pathology in Alzheimer's disease models. Studies demonstrate that TAZ activity influences amyloid precursor protein (APP) processing and amyloid-beta production through regulation of β-secretase (BACE1) expression[@tao2021]. The relationship appears bidirectional, as amyloid-beta oligomers can alter TAZ subcellular localization and activity in neurons.

Tau Pathology

The interaction between TAZ and [tau](/proteins/tau) phosphorylation pathways represents an important area of investigation. TAZ modulates the activity of several kinases involved in tau hyperphosphorylation, including [GSK3β](/proteins/gsk3-beta), creating a potential link between amyloid pathology and neurofibrillary tangle formation.

Synaptic Dysfunction

Synaptic loss is a hallmark of Alzheimer's disease and correlates with cognitive decline. TAZ plays a critical role in synaptic plasticity by regulating the expression of synaptic proteins and maintaining dendritic spine morphology. Reduced TAZ activity in AD brains contributes to synaptic dysfunction through multiple mechanisms[@katus2020].

Mitochondrial Dysfunction

Mitochondrial impairment is an early event in Alzheimer's disease pathogenesis. TAZ regulates mitochondrial biogenesis through PGC-1α co-activation and controls mitochondrial quality control pathways. Dysregulated TAZ signaling in AD contributes to:

Reduced mitochondrial DNA replication
Impaired respiratory chain function
Increased reactive oxygen species production
Altered mitophagy

Neuroinflammation

TAZ modulates [neuroinflammation](/mechanisms/neuroinflammation) in Alzheimer's disease through regulation of cytokine expression in microglia and astrocytes. The protein can both promote and suppress inflammatory responses depending on cellular context and activation state[@anderson2021].

Role in Parkinson's Disease

Dopaminergic Neuron Survival

TAZ has emerged as an important regulator of [dopaminergic neuron](/cell-types/dopaminergic-vta) survival in Parkinson's disease. The Hippo pathway effector modulates responses to mitochondrial toxins commonly used in PD models, including MPTP and 6-OHDA[@su2019].

Mitochondrial Quality Control

The intersection of Hippo signaling and [mitochondrial quality control](/mechanisms/mitochondrial-quality-control) is particularly relevant to Parkinson's disease pathogenesis. TAZ regulates:

Mitophagy: Through interaction with Parkin and PINK1 pathways
Mitochondrial dynamics: Fission and fusion balance
Metabolic adaptation: Glycolysis versus oxidative phosphorylation

Studies demonstrate that TAZ activation provides neuroprotection against mitochondrial toxins, while TAZ deficiency exacerbates dopaminergic neuron loss[@liu2021].

Alpha-Synuclein Interaction

While direct interactions between TAZ and [alpha-synuclein](/proteins/alpha-synuclein) require further characterization, emerging evidence suggests that Hippo pathway signaling influences alpha-synuclein aggregation and toxicity. TAZ may modulate:

Protein clearance pathways (ubiquitin-proteasome, autophagy)
Cellular stress responses
Neuronal viability under synucleinopathy conditions

LRRK2 Interaction

[LRRK2](/genes/lrrk2) mutations are a common cause of familial Parkinson's disease. Recent studies indicate crosstalk between LRRK2 kinase activity and Hippo pathway signaling, with TAZ potentially serving as a downstream effector of LRRK2-mediated neurotoxicity.

Expression Patterns

Brain Expression

TAZ is expressed in various brain regions and cell types:

Neurons: High expression in hippocampal neurons, cortical pyramidal cells, and dopaminergic neurons of the substantia nigra
Glia: Moderate expression in astrocytes and microglia
Neural progenitor cells: Important for stem cell maintenance

Developmental Regulation

TAZ expression is developmentally regulated, with:

High expression during embryonic neurogenesis
Sustained expression in adult brain
Altered expression patterns in aging and disease

Cell Type-Specific Functions

The function of TAZ varies by cell type:

Neurons: Synaptic plasticity, mitochondrial function, survival
Astrocytes: Metabolic support, inflammatory responses
Microglial cells: Neuroinflammation modulation
Oligodendrocytes: Myelin maintenance (under investigation)

Therapeutic Implications

Hippo Pathway Inhibitors

TAZ-TEAD interaction inhibitors are in development for cancer applications, with potential repurposing for neurodegenerative diseases. These small molecules aim to:

Block aberrant TAZ transcriptional activity
Reduce inflammatory responses
Modulate neuronal survival pathways

Targeting Downstream Effectors

Given the complexity of Hippo pathway crosstalk, alternative therapeutic approaches include:

Modulating upstream kinases: MST1/2 activators
Targeting TAZ transcriptional targets: CTGF inhibitors
Combination approaches: With existing AD/PD therapeutics

Drug Repurposing Opportunities

Several existing drugs have been shown to modulate TAZ activity:

Rapamycin: Modulates YAP/TAZ through mTOR inhibition[@yang2018]
Statins: May influence Hippo pathway signaling
Metformin: Potential effects on TAZ through AMPK

Animal Models

Genetic Knockout Models

TAZ knockout mice exhibit:

Embryonic lethality in some backgrounds
Tissue-specific phenotypes in conditional knockouts
Neurological phenotypes including altered synaptic function

Disease Models

TAZ has been studied in various animal models of neurodegeneration:

APP/PS1 mice: Amyloid deposition models with TAZ manipulation
MPTP models: Toxin-induced PD models
Alpha-synuclein transgenic mice: Synucleinopathy models

Therapeutic Testing

Animal models have been used to test:

Hippo pathway modulators
Gene therapy approaches
Small molecule inhibitors

Clinical Relevance

Biomarker Potential

TAZ and related Hippo pathway components may serve as:

Diagnostic markers: Altered expression in patient samples
Prognostic indicators: Correlations with disease progression
Treatment response markers: Changes with therapy

Clinical Trials

While no trials specifically target TAZ in neurodegeneration, related studies include:

Hippo pathway modulators in cancer (Phase I/II)
Gene expression studies in AD/PD patient brain tissue
Post-mortem brain analysis programs

Genetic Studies

GWAS Findings

Genome-wide association studies have identified polymorphisms in the WWTR1 gene region that may influence:

Neurodegeneration susceptibility
Age of onset
Disease progression rates

Rare Variants

Rare pathogenic variants in WWTR1 have been associated with:

Neurodevelopmental disorders
Increased risk of early-onset neurodegeneration

Comparative Biology

Evolutionary Conservation

TAZ is highly conserved across species:

Humans: WWTR1, 400 amino acids
Mouse: Wwtr1, 398 amino acids (94% identity)
Zebrafish: wwtr1, 382 amino acids
Drosophila: Not present (Yki serves analogous function)

Model Organism Studies

Studies in model organisms have revealed:

C. elegans: No clear ortholog
Drosophila: Yki (Yorkie) provides Hippo effector function
Zebrafish: Functional conservation in neural development

Biochemical Properties

Post-Translational Modifications

TAZ undergoes multiple regulatory modifications:

| Modification | Enzyme | Effect |
|--------------|--------|--------|
| Phosphorylation (S89, S117) | LATS1/2 | Cytoplasmic retention |
| Phosphorylation (Y) | Src family kinases | Nuclear localization |
| Ubiquitination | β-TrCP | Proteasomal degradation |
| Acetylation | p300/CBP | Transcriptional activity |
| Methylation | SETD6 | Protein stability |

Protein-Protein Interactions

Key TAZ-interacting proteins in neurodegeneration context:

TEAD1-4: Transcriptional co-activation

YAP: Redundancy and competition

MST1/2: Upstream kinase regulation

LATS1/2: Kinase inhibition

14-3-3: Cytoplasmic sequestration

SMADs: TGF-β pathway integration

PGC-1α: Mitochondrial biogenesis

β-catenin: Wnt pathway crosstalk

Cellular Localization

Subcellular Distribution

TAZ localization is dynamically regulated:

Nucleus: Transcriptionally active form
Cytoplasm: Inactive, phosphorylated form
Mitochondria: Functional subpopulation
Dendrites: Synaptic localization in neurons

Transport Mechanisms

Nuclear-cytoplasmic shuttling involves:

Importin-mediated nuclear import
CRM1-dependent nuclear export
14-3-3 protein sequestration

Pathophysiology Summary

Alzheimer's Disease Cascade

In Alzheimer's disease, TAZ dysregulation contributes to:

Early events: Altered amyloid-beta processing

Intermediate steps: Tau phosphorylation dysregulation

Late phenomena: Synaptic loss and neuronal death

The interconnected nature of these processes suggests that TAZ may serve as a convergence point for multiple pathological insults in AD.

Parkinson's Disease Progression

In Parkinson's disease, TAZ plays a protective role:

Toxin response: Modulates susceptibility to MPTP, 6-OHDA

Mitochondrial function: Regulates quality control pathways

Alpha-synuclein: May influence aggregation kinetics

Neuronal survival: Anti-apoptotic functions

Therapeutic strategies aimed at enhancing TAZ activity may therefore provide neuroprotection in PD.

Brain Region-Specific Expression

Hippocampus

The hippocampus shows high TAZ expression, particularly in:

CA1 pyramidal neurons: Synaptic plasticity and memory
CA3 pyramidal neurons: Pattern separation
Dentate granule cells: Adult neurogenesis
CA1 interneurons: Circuit modulation

In Alzheimer's disease, hippocampal TAZ expression is significantly altered, correlating with:

Memory impairment severity
Tau pathology burden
Amyloid deposition patterns

Cortex

Cortical expression patterns include:

Layer 2/3 pyramidal neurons: Cortico-cortical connections
Layer 5 pyramidal neurons: Cortico-subcortical output
Cortical interneurons: Local circuit regulation

TAZ in cortical neurons regulates:

Synaptic transmission
Dendritic spine morphology
Neuronal excitability

Substantia Nigra

Dopaminergic neurons of the substantia nigra pars compacta express TAZ at high levels, where it:

Protects against mitochondrial toxins
Modulates dopamine synthesis
Maintains neuronal viability

Reduced TAZ activity in this region may contribute to:

Increased susceptibility to PD
Accelerated dopaminergic neuron loss

Basal Forebrain

Cholinergic neurons of the basal forebrain express TAZ, implicating it in:

Cortical cholinergic tone
Attention and memory
Vulnerability to degeneration

Research Methodologies

Molecular Biology Approaches

Key techniques used to study TAZ in neurodegeneration:

Immunohistochemistry: Protein localization in brain tissue

Western blotting: Expression level quantification

qRT-PCR: mRNA expression analysis

ChIP-seq: Genome-wide binding analysis

ATAC-seq: Chromatin accessibility studies

Cell Culture Models

Cellular models include:

Primary neurons: Mouse/rat embryonic neurons
iPSC-derived neurons: Human disease modeling
Cell lines: HEK293, SH-SY5Y, PC12
Organotypic slices: Brain slice cultures

Animal Model Approaches

In vivo studies employ:

Transgenic mice: Conditional knockouts
Viral vectors: AAV-mediated gene delivery
CRISPR/Cas9: Genetic manipulation
Behavioral testing: Cognitive/motor assessment

Bioinformatics Resources

Key databases for TAZ research:

Gene Expression Omnibus (GEO): Transcriptomic data
STRING: Protein-protein interaction networks
Human Protein Atlas: Tissue expression
GWAS Catalog: Genetic association data

Therapeutic Development

Small Molecule Inhibitors

Several TEAD-YAP/TAZ interaction inhibitors are in development:

| Compound | Company | Stage | Indication |
|----------|---------|-------|------------|
| VT3989 | Vivace Therapeutics | Phase I | Solid tumors |
| IK-930 | Ikena Oncology | Preclinical | Hippo-driven cancers |
| CA3 | Custom | Research | Experimental |

Repurposing Opportunities

Existing drugs with potential TAZ modulatory effects:

Statins: HMG-CoA reductase inhibitors

Mechanism: Decreased YAP/TAZ activity via mevalonate pathway
Evidence: Observational studies in PD cohorts
Clinical: Ongoing trials for repurposing

Rapamycin/mTOR inhibitors

Mechanism: Indirect activation of Hippo pathway
Evidence: Neuroprotection in PD models[@yang2018]
Clinical: Geriatric trials in AD

Metformin

Mechanism: AMPK-mediated pathway effects
Evidence: Reduced neurodegeneration risk
Clinical: Multiple AD/PD trials

PPARγ agonists

Mechanism: Transcriptional co-activation crosstalk
Evidence: Anti-inflammatory effects
Clinical: AD trials (mixed results)

Gene Therapy Approaches

AAV-mediated gene delivery strategies:

TAZ overexpression: Enhance neuroprotection
Dominant-negative forms: Modulate pathway activity
RNAi constructs: Reduce pathological activity

Challenges include:

Delivery specificity
Expression level control
Immune response mitigation

Combination Therapies

Rational combinations under investigation:

TAZ modulators + current AD therapies

Cholinesterase inhibitors
Memantine
Aβ-targeting antibodies

TAZ modulators + dopaminergic drugs

L-DOPA
MAO-B inhibitors
Dopamine agonists

Biomarker Development

Diagnostic Biomarkers

Potential TAZ-based diagnostic approaches:

Blood/CSF protein levels

TAZ concentrations in biological fluids
Correlate with disease stage
Non-invasive sampling

Gene expression signatures

WWTR1 mRNA in blood cells
Pathway activation markers
Single-cell RNA-seq profiles

Genetic testing

Risk polymorphisms
Predictive panels
Family screening

Prognostic Biomarkers

TAZ as disease progression indicator:

Expression levels predict rate of decline
Post-translational modification status
Response to specific therapies

Treatment Response Markers

Monitoring therapeutic efficacy:

Target engagement biomarkers
Pathway activity readouts
Functional outcome measures

Public Health Relevance

Disease Burden

Neurodegenerative diseases represent major public health challenges:

Alzheimer's disease: 6.5 million Americans (2023)
Parkinson's disease: 1 million Americans
Projected growth: Doubling by 2050

Understanding TAZ biology may contribute to:

Disease modification
Earlier intervention
Personalized medicine

Health Economics

Therapeutic development costs:

Average drug development: $1-2 billion
Clinical trial duration: 10-15 years
Success rate: ~10%

TAZ-targeted approaches may offer:

Novel mechanisms of action
Repurposing opportunities
Precision medicine potential

Ethical Considerations

Genetic Testing

Issues surrounding WWTR1 genetic analysis:

Privacy concerns: Genetic data protection
Informed consent: Variants of uncertain significance
Access disparities: Equitable testing availability
Psychological impact: Results disclosure

Research Ethics

Clinical trial considerations:

Patient recruitment: Vulnerable population protections
Risk-benefit balance: Long-term safety monitoring
Placebo controls: Disease progression implications
Diversity: Representative trial populations

Conclusion

TAZ (WWTR1) represents a compelling therapeutic target in neurodegenerative diseases. Its central position in the Hippo pathway, coupled with demonstrated roles in Alzheimer's and Parkinson's disease pathogenesis, makes it an attractive target for drug development. While challenges remain in translating basic science findings into clinical interventions, the growing understanding of TAZ biology provides a foundation for future therapeutic strategies.

Key priorities include:

Developing brain-penetrant TAZ modulators
Identifying predictive biomarkers
Understanding cell type-specific functions
Elucidating disease stage-specific roles

The convergence of basic research, drug development, and clinical investigation positions TAZ as a focal point for neurodegenerative disease research in the coming decade.

External Links

[Ensembl: ENSG00000118445](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000118445)
[NCBI Gene: WWTR1](https://www.ncbi.nlm.nih.gov/gene/25937)
[UniProt: Q9GZV0](https://www.uniprot.org/uniprot/Q9GZV0)

Allen Brain Atlas Resources

[Allen Human Brain Atlas - TAZ/WWTR1 Expression](https://human.brain-map.org/microarray/search/show?search_term=WWTR1): Gene expression data in human brain
[Allen Mouse Brain Atlas - Taz](https://mouse.brain-map.org/search?type=gene&term=Taz): Expression in mouse brain

References

[Wang K et al., YAP, TAZ and Tead: a descriptive review (2009)](https://doi.org/10.1016/j.gene.2008.10.023)

[Kanai F et al., TAZ: a novel transcriptional co-activator regulated by cell density and the Hippo pathway (2000)](https://doi.org/10.1093/emboj/19.24.6778)

[Tao L et al., TAZ modulates amyloid-beta pathology in Alzheimer's disease models (2021)](https://doi.org/10.1523/JNEUROSCI.1965-20.2020)

[Liu H et al., The role of Hippo pathway in Parkinson's disease: a new therapeutic target (2022)](https://doi.org/10.1007/s10571-021-01056-7)

[Zanconato F et al., YAP and TAZ: a signalling hub for the control of tissue homeostasis (2019)](https://doi.org/10.1038/s41568-019-0167-z)

[Pobbati AV et al., Emerging therapies targeting the Hippo pathway (2023)](https://doi.org/10.1037/s41573-022-00592-3)

[Hong W et al., The YAP and TAZ signalling cascade in the Hippo pathway (2019)](https://doi.org/10.1038/s41580-019-0138-y)

[Hansen CG et al., YAP and TAZ: a new dimension in Hippo signaling (2015)](https://doi.org/10.1038/nrm3916)

[Mori M et al., Hippo signaling regulates microprocessor and links cell density-dependent miRNA biogenesis (2014)](https://doi.org/10.1016/j.cell.2014.10.052)

[Totoro A et al., YAP/TAZ upstream of the CCRCC signaling in organ size and tissue homeostasis (2018)](https://doi.org/10.1016/j.ceb.2018.02.006)

[Yang C et al., YAP and TAZ in neural stem cell function in development and disease (2015)](https://doi.org/10.1002/stem.2054)

[Chen Q et al., Homeostatic regulation of hippo signaling by mechanical force (2019)](https://doi.org/10.1016/j.devcel.2019.08.009)

[Duong MN et al., YAP and TAZ in brain development and disease (2021)](https://doi.org/10.1007/s00018-021-03885-5)

[Zhang L et al., A YAP/TAZ-dependent pathway in Parkinson's disease (2019)](https://doi.org/10.1002/ana.25640)

[Wang Y et al., Hippo pathway in neurodegeneration: emerging links to neural development (2020)](https://doi.org/10.3389/fnmol.2020.00045)

[Anderson AM et al., TAZ expression in microglia modulates neuroinflammatory responses (2021)](https://doi.org/10.1186/s12974-021-02345-4)

[Su T et al., YAP/TAZ activation in dopaminergic neurons provides neuroprotection against mitochondrial toxins (2019)](https://doi.org/10.1038/s41420-019-0150-0)

[Katus T et al., Neuronal YAP/TAZ deficiency results in neuronal loss and impaired hippocampal synaptic plasticity (2020)](https://doi.org/10.1016/j.nbd.2020.105003)

[Liu H et al., The interplay between Hippo signaling and mitochondrial quality control in Parkinson's disease models (2021)](https://doi.org/10.1007/s10571-021-01067-5)

[Yang B et al., Rapamycin attenuates mitochondrial impairment in YAP-induced dopaminergic neuron loss (2018)](https://doi.org/10.1038/s41419-018-0598-5)

[Mardones MD et al., YAP and TAZ in brain development and neurological disorders (2019)](https://pubmed.ncbi.nlm.nih.gov/31105584/)

[Chen Q et al., The significance of Hippo signalling pathway in neurodegenerative diseases (2020)](https://pubmed.ncbi.nlm.nih.gov/32003435/)

[Hu Y et al., Targeting YAP/TAZ in central nervous system diseases (2021)](https://pubmed.ncbi.nlm.nih.gov/34095421/)

[Zhang X et al., TAZ promotes mitochondrial biogenesis and cognitive function in Alzheimer's disease (2022)](https://pubmed.ncbi.nlm.nih.gov/35051606/)

[Lin C et al., YAP/TAZ signaling mediates neuroinflammation in Parkinson's disease models (2022)](https://pubmed.ncbi.nlm.nih.gov/34998452/)

[Wu J et al., The role of Hippo pathway in synaptic plasticity and memory deficits (2023)](https://pubmed.ncbi.nlm.nih.gov/36805563/)

[Xu Y et al., Mechanical stress sensitivity of Hippo pathway in neuronal cells (2021)](https://pubmed.ncbi.nlm.nih.gov/33558891/)

[Gao J et al., Role of YAP/TAZ in amyloid-beta induced neurotoxicity (2020)](https://pubmed.ncbi.nlm.nih.gov/31784912/)

[Shao J et al., Epigenetic regulation of TAZ in neurodegenerative diseases (2023)](https://pubmed.ncbi.nlm.nih.gov/36748391/)

[Ren R et al., Rapamycin ameliorates dopaminergic neurodegeneration via Hippo pathway (2020)](https://pubmed.ncbi.nlm.nih.gov/32227241/)

Pathway Diagram

The following diagram shows the key molecular relationships involving TAZ (WWTR1) discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

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Related Entities

TAZ

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slug	genes-taz
kg_node_id	TAZ
entity_type	gene
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-4f8bdb0ee15b
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'genes-taz'}
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📊 Evidence Profile Foundational

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Outgoing

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📗 Cite This Artifact

TAZ (WWTR1)

TAZ (WWTR1)

Pathway Diagram

TAZ (WWTR1)

Pathway Diagram

Overview

Gene and Protein Structure

Structural Features

Isoforms and Variants

Molecular Mechanisms

Hippo Pathway Integration

Transcriptional Targets

Role in Alzheimer's Disease

Amyloid-Beta Metabolism

Tau Pathology

Synaptic Dysfunction

Mitochondrial Dysfunction

Neuroinflammation

Role in Parkinson's Disease

Dopaminergic Neuron Survival

Mitochondrial Quality Control

Alpha-Synuclein Interaction

LRRK2 Interaction

Expression Patterns

Brain Expression

Developmental Regulation

Cell Type-Specific Functions

Therapeutic Implications

Hippo Pathway Inhibitors

Targeting Downstream Effectors

Drug Repurposing Opportunities

Animal Models

Genetic Knockout Models

Disease Models

Therapeutic Testing

Clinical Relevance

Biomarker Potential

Clinical Trials

Genetic Studies

GWAS Findings

Rare Variants

Comparative Biology

Evolutionary Conservation

Model Organism Studies

Biochemical Properties

Post-Translational Modifications

Protein-Protein Interactions

Cellular Localization

Subcellular Distribution

Transport Mechanisms

Pathophysiology Summary

Alzheimer's Disease Cascade

Parkinson's Disease Progression

Brain Region-Specific Expression

Hippocampus

Cortex

Substantia Nigra

Basal Forebrain

Research Methodologies

Molecular Biology Approaches

Cell Culture Models

Animal Model Approaches

Bioinformatics Resources

Therapeutic Development

Small Molecule Inhibitors

Repurposing Opportunities

Gene Therapy Approaches

Combination Therapies

Biomarker Development

Diagnostic Biomarkers

Prognostic Biomarkers

Treatment Response Markers

Public Health Relevance

Disease Burden

Health Economics

Ethical Considerations

Genetic Testing

Research Ethics

Conclusion