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WWTR1 Protein
<div class="infobox infobox-protein"> <div class="infobox-header">WWTR1 Protein (TAZ)</div>
Overview
WWTR1 Protein is a protein encoded by the [WWTR1](/genes/wwtr1) gene. This page describes its structure, normal nervous system function, role in neurodegenerative disease, and potential as a therapeutic target. [@zhang2020]
WWTR1 (WW Domain Containing Transcription Regulator 1), also known as TAZ (Transcriptional Coactivator with PDZ-binding motif), is a 400-amino acid protein containing:
...
WWTR1 Protein
<div class="infobox infobox-protein"> <div class="infobox-header">WWTR1 Protein (TAZ)</div>
Overview
WWTR1 Protein is a protein encoded by the [WWTR1](/genes/wwtr1) gene. This page describes its structure, normal nervous system function, role in neurodegenerative disease, and potential as a therapeutic target. [@zhang2020]
WWTR1 (WW Domain Containing Transcription Regulator 1), also known as TAZ (Transcriptional Coactivator with PDZ-binding motif), is a 400-amino acid protein containing:
WW domain: Mediates protein-protein interactions by binding to proline-rich motifs
PDZ-binding motif: Interacts with PDZ domain-containing proteins
Transactivation domain: C-terminal domain for transcriptional coactivation
TEA domain (TEAD-binding domain): Binds to TEAD transcription factors
The protein functions primarily as a transcriptional coactivator, lacking DNA-binding capability but modulating gene expression through interactions with various transcription factors [1](https://doi.org/10.1016/j.tibs.2011.03.005).
Normal Function in the Nervous System
In the nervous system, WWTR1/TAZ is involved in:
Hippo signaling pathway: Key effector that regulates neuronal survival and growth
Neural stem cell maintenance: Controls stem cell proliferation and differentiation
Axon regeneration: Modulates the response to neuronal injury
Synaptic plasticity: Influences dendritic spine formation and synaptic function
Transcriptional regulation: Coactivates genes involved in neuroprotection
TAZ is expressed in neural progenitor cells and mature [neurons](/entities/neurons), with roles in brain development and homeostasis [2](https://doi.org/10.1016/j.neuroscience.2015.06.038).
Role in Disease
Alzheimer's Disease (AD)
TAZ/Hippo signaling is dysregulated in AD brain tissue
The protein interacts with [tau](/proteins/tau) pathology and may modulate tau toxicity
Neuroprotective signaling through YAP/TAZ is impaired in AD
May contribute to synaptic dysfunction through altered transcription [3](https://pubmed.ncbi.nlm.nih.gov/28757465/)
Parkinson's Disease (PD)
Hippo pathway activation is observed in PD models
TAZ may protect against dopaminergic neuron death
Interactions with [alpha-synuclein](/proteins/alpha-synuclein) pathology are being investigated
Modulates ER stress response in dopaminergic neurons
Stroke and Ischemia
YAP/TAZ signaling is protective in cerebral ischemia
Activation promotes neuronal survival after stroke
Potential therapeutic target for stroke intervention
Neurodevelopmental Disorders
Dysregulated Hippo/TAZ signaling contributes to impaired brain development
Associated with intellectual disability in some cases
Therapeutic Targeting
Hippo pathway modulators: Small molecules activating YAP/TAZ are under development
Gene therapy: Viral vectors delivering TAZ for neuroprotection
No direct TAZ-targeted drugs are currently approved for neurodegeneration
Key Publications
[TAZ as a transcriptional coactivator in Hippo signaling (2011)](https://doi.org/10.1016/j.tibs.2011.03.005)
[Role of TAZ in neural development and disease (2015)](https://doi.org/10.1016/j.neuroscience.2015.06.038)
[Hippo pathway in Alzheimer's disease (2017)](https://pubmed.ncbi.nlm.nih.gov/28757465/)
[YAP/TAZ in cerebral ischemia and neuroprotection (2018)](https://doi.org/10.1161/STROKEAHA.117.019234)