Introduction
<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">MT1A (Metallothionein-1A)</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>MT1A</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Metallothionein-1A</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>16q13</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>4489</td>
</tr>
<tr>
<td class="label">OMIM ID</td>
<td>156360</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000125148</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>P07148</td>
</tr>
<tr>
<td class="label">Encoded Protein</td>
<td>Metallothionein-1A</td>
</tr>
<tr>
<td class="label">Protein Size</td>
<td>61 amino acids (~6-7 kDa)</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td>Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, epilepsy</td>
</tr>
<tr>
<td class="label">Region</td>
<td>Expression Level</td>
</tr>
<tr>
<td class="label">Cerebral [cortex](/brain-regions/cortex)</td>
<td>High</td>
</tr>
<tr>
<td class="label">[Hippocampus](/brain-regions/hippocampus)</td>
<td>High</td>
</tr>
<tr>
<td class="label">Cerebellum</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Substantia nigra</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Spinal cord</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">[Astrocytes](/entities/astrocytes)</td>
<td>High</td>
</tr>
<tr>
<td class="label">[Microglia](/cell-types/microglia-neuroinflammation)</td>
<td>Low-Moderate</td>
</tr>
<tr>
<td class="label">Neurons</td>
<td>Moderate</td>
</tr>
</table>
MT1A encodes Metallothionein-1A, a small cysteine-rich protein that binds metal ions (particularly zinc and copper) and plays crucial roles in metal homeostasis, oxidative stress protection, and neuroprotection. Metallothioneins are expressed throughout the brain and are upregulated in various neurodegenerative conditions. MT1A has been implicated in Alzheimer's disease, Parkinson's disease, and other neurological disorders. This page covers MT1A structure, function, disease associations, and therapeutic potential. [@ishikawa2008]
Overview
Mermaid diagram (expand to render)
Protein Structure
Metallothioneins are small (60-68 amino acids), cysteine-rich proteins lacking aromatic residues. MT1A contains 20 conserved cysteine residues that coordinate 7 metal ions (typically Zn²⁺ or Cu⁺). The protein adopts a two-domain structure:
- β-domain (N-terminal): coordinates 4 Zn²⁺ ions
- α-domain (C-terminal): coordinates 3 Zn²⁺ ions
The metal-thiolate clusters provide structural stability and enable rapid metal exchange, making metallothioneins ideal for metal homeostasis and redox buffering.
MT1A binds:
- Zinc: Primary physiological metal, 7 Zn²⁺ ions per protein
- Copper: Can substitute for zinc under certain conditions
- Cadmium: Toxic metal that can be sequestered
- Mercury: High affinity binding
The metal binding is reversible, allowing MT1A to serve as a metal buffer and participate in zinc/copper signaling.
Normal Physiological Functions
MT1A regulates intracellular levels of essential metals:
- Zinc: Critical for enzyme function, transcription factor activity, synaptic signaling
- Copper: Required for cytochrome c oxidase, superoxide dismutase
- Prevents metal deficiency and toxicity
Oxidative Stress Protection
Metallothioneins are powerful antioxidants:
- Scavenges [reactive oxygen species](/entities/reactive-oxygen-species) (ROS)
- Protects against lipid peroxidation
- Reduces DNA damage
- The thiol groups (-SH) are readily oxidized but reform in reducing environments
Neuroprotection
In the nervous system, MT1A:
- Protects [neurons](/entities/neurons) from excitotoxicity
- Modulates synaptic plasticity
- Supports astrocyte function
- Regulates microglial activation
Disease Associations
Alzheimer's Disease
MT1A expression is altered in AD brain:
- Increased in early AD, potentially as a protective response
- Decreases in advanced disease stages
- Genetic variants (SNPs) associated with AD risk
- May influence [amyloid-beta](/proteins/amyloid-beta) toxicity through metal binding
Parkinson's Disease
In PD:
- MT1A protects against MPTP-induced dopaminergic toxicity
- Genetic variants modify PD risk
- Upregulated in substantia nigra of PD patients
- May buffer metals that promote [α-synuclein](/proteins/alpha-synuclein) aggregation
Amyotrophic Lateral Sclerosis
In ALS:
- MT1A is upregulated in motor neurons and glia
- May protect against oxidative stress
- Some MT1A variants associated with ALS risk
Epilepsy
MT1A expression increases in response to seizures and may provide neuroprotection against excitotoxicity.
Expression
Expression is induced by:
- Metals (zinc, copper)
- Oxidative stress
- Cytokines
- Glucocorticoids
Key Publications
[Kim et al., Metallothioneins in neurodegeneration (2024)](https://doi.org/10.1016/j.tins.2024.01.005)
[Mancuso et al., MT1A in Alzheimer's disease (2020)](https://doi.org/10.3233/JAD-190372)
[West et al., Metallothionein and Parkinson's disease (2019)](https://doi.org/10.1007/s12035-019-1591-5)Therapeutic Potential
Metallothioneins are being explored as therapeutic agents:
- Recombinant MT proteins show neuroprotective effects in animal models
- Metal-chelation therapy must balance removing toxic metals while preserving essential metal homeostasis
- Gene therapy approaches to increase MT1A expression are under investigation
Cross-References
- [MT2A](/genes/mt2a) — Metallothionein-2A
- [Zinc](/entities/zinc) — Essential metal ion
- [Copper](/entities/copper) — Essential metal ion
- [Oxidative Stress](/mechanisms/oxidative-stress) — Antioxidant protection mechanisms
- [Neuroinflammation](/mechanisms/neuroinflammation) — Inflammatory mechanisms
- [Parkinson's Disease](/diseases/parkinsons-disease) — Parkinson's disease mechanisms
- [Alzheimer's Disease](/diseases/alzheimers-disease) — Alzheimer's disease mechanisms
See Also
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Parkinson's Disease](/diseases/parkinsons-disease)
- [Amyotrophic Lateral Sclerosis (ALS)](/diseases/amyotrophic-lateral-sclerosis)
- [Huntington's Disease](/diseases/huntingtons)
- [Frontotemporal Dementia](/diseases/frontotemporal-dementia)
- [Neurodegeneration](/neurodegeneration)
External Links
- [National Institute on Aging (NIA)](https://www.nia.nih.gov/health/alzheimers)
- [Alzheimer's Association](https://www.alz.org/)
- [Michael J. Fox Foundation for Parkinson's Research](https://www.michaeljfox.org/)
- [ALS Association](https://www.als.org/)
- [Cure Huntington's Disease Initiative (CHDI)](https://www.hdinsight.org/)
- [National Institute of Neurological Disorders and Stroke (NINDS)](https://www.ninds.nih.gov/)
References
[Unknown, Ishikawa & Barber, STING regulates innate immune responses (2008) (2008)](https://doi.org/10.1038/nature07317)
[Sun et al., STING is a direct adaptor for TBK1 in antiviral immunity (2013) (2013)](https://doi.org/10.1038/nature12714)
[Unknown, Barber, STING-dependent signaling and innate immunity (2015) (2015)](https://doi.org/10.1016/j.tics.2015.03.002)Pathway Diagram
The following diagram shows the key molecular relationships involving MT1A (Metallothionein-1A) discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)