Introduction <table class="infobox infobox-gene">Gene Symbol </td>Full Name </td>Chromosomal Location </td>NCBI Gene ID </td>OMIM ID </td>Ensembl ID </td>UniProt ID </td>Encoded Protein </td>Protein Size </td>Associated Diseases </td>
...
Introduction <table class="infobox infobox-gene">Gene Symbol </td>Full Name </td>Chromosomal Location </td>NCBI Gene ID </td>OMIM ID </td>Ensembl ID </td>UniProt ID </td>Encoded Protein </td>Protein Size </td>Associated Diseases </td>
MT2A encodes Metallothionein-2A, a member of the metallothionein family of metal-binding proteins. Like other metallothioneins, MT2A plays essential roles in metal homeostasis, oxidative stress protection, and cellular defense. MT2A is highly expressed in the brain and is upregulated in response to various cellular stresses. It has been implicated in Alzheimer's disease, Parkinson's disease, and other neurodegenerative conditions. This page covers MT2A structure, function, disease associations, and therapeutic potential. [@coyle1995]
Overview
Mermaid diagram (expand to render)
Structure MT2A is highly homologous to other metallothioneins:
61 amino acids in length
20 cysteine residues
Two-domain structure (α and β domains)
Binds 7 zinc or other metal ions
The protein has metal-thiolate clusters that provide structural stability and enable rapid metal exchange.
Normal Physiological Functions
MT2A regulates intracellular zinc and copper levels:
Buffers cytosolic zinc concentrations
Participates in zinc trafficking
Protects against metal toxicity
Antioxidant Defense MT2A is a potent antioxidant:
Scavenges [reactive oxygen species](/entities/reactive-oxygen-species)
Protects against lipid peroxidation
Reduces metal-catalyzed oxidative damage
Immunomodulation MT2A modulates immune responses:
Regulates cytokine production
Affects microglial activation
Modulates inflammatory responses
Disease Associations
Alzheimer's Disease MT2A in AD:
Upregulated in early AD brain
May buffer metals involved in [Aβ](/proteins/amyloid-beta) aggregation
Genetic variants associated with AD risk
Parkinson's Disease In PD:
Protects dopaminergic [neurons](/entities/neurons) from oxidative stress
Upregulated in substantia nigra of PD patients
May influence [α-synuclein](/proteins/alpha-synuclein) aggregation
Epilepsy MT2A expression increases following seizures and may provide neuroprotection against excitotoxicity.
Expression MT2A is expressed in:
Brain (neurons, [astrocytes](/entities/astrocytes), microglia)
Liver
Kidney
Heart
Immune cells
Expression is induced by:
Metals (zinc, copper)
Oxidative stress
Cytokines
Glucocorticoids
Key Publications
[Kim et al., Metallothionein neuroprotection (2024)](https://doi.org/10.1016/j.tins.2024.01.005)
[Mancuso et al., MT isoforms in AD (2020)](https://doi.org/10.3233/JAD-190372)
Therapeutic Potential MT2A is being investigated as a therapeutic target:
Metal-based therapies must consider metallothionein interactions
Gene therapy approaches to increase MT2A expression
Small molecule inducers of metallothionein expression
Cross-References
[MT1A](/genes/mt1a) — Metallothionein-1A
[Zinc](/entities/zinc) — Essential metal ion
[Oxidative Stress](/mechanisms/oxidative-stress) — Antioxidant mechanisms
[Neuroinflammation](/mechanisms/neuroinflammation) — Inflammatory mechanisms
[Parkinson's Disease](/diseases/parkinsons-disease) — PD 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 on Neurological Disorders and Stroke (NINDS)](https://www.ninds.nih.gov/)
References
[Coyle et al., Metallothionein in neurodegeneration (1995) (1995)](https://pubmed.ncbi.nlm.nih.gov/8543772/)
[Mirault et al., Metallothionein expression in neurodegenerative diseases (1999) (1999)](https://pubmed.ncbi.nlm.nih.gov/10543583/)
[West et al., Argonaute proteins in RNA interference (2004) (2004)](https://doi.org/10.1016/j.molmed.2004.09.006)
[Iwasaki et al., Argonaute function in the nervous system (2015) (2015)](https://doi.org/10.1016/j.tics.2015.06.010) Show full description