Molecular basis for certain neuroprotective effects of thyroid hormone

Hung-Yun Lin, Faith B Davis, Mary K Luidens, Shaker A Mousa, James H Cao, Min Zhou, Paul J Davis

Research output: Contribution to journalReview article

Abstract

The pathophysiology of brain damage that is common to ischemia-reperfusion injury and brain trauma include disodered neuronal and glial cell energetics, intracellular acidosis, calcium toxicity, extracellular excitotoxic glutamate accumulation, and dysfunction of the cytoskeleton and endoplasmic reticulum. The principal thyroid hormones, 3,5,3'-triiodo-l-thyronine (T(3)) and l-thyroxine (T(4)), have non-genomic and genomic actions that are relevant to repair of certain features of the pathophysiology of brain damage. The hormone can non-genomically repair intracellular H(+) accumulation by stimulation of the Na(+)/H(+) exchanger and can support desirably low [Ca(2+)](i.c.) by activation of plasma membrane Ca(2+)-ATPase. Thyroid hormone non-genomically stimulates astrocyte glutamate uptake, an action that protects both glial cells and neurons. The hormone supports the integrity of the microfilament cytoskeleton by its effect on actin. Several proteins linked to thyroid hormone action are also neuroprotective. For example, the hormone stimulates expression of the seladin-1 gene whose gene product is anti-apoptotic and is potentially protective in the setting of neurodegeneration. Transthyretin (TTR) is a serum transport protein for T(4) that is important to blood-brain barrier transfer of the hormone and TTR also has been found to be neuroprotective in the setting of ischemia. Finally, the interesting thyronamine derivatives of T(4) have been shown to protect against ischemic brain damage through their ability to induce hypothermia in the intact organism. Thus, thyroid hormone or hormone derivatives have experimental promise as neuroprotective agents.

Original languageEnglish
Pages (from-to)29
JournalFrontiers in Molecular Neuroscience
Volume4
DOIs
Publication statusPublished - 2011
Externally publishedYes

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Neuroprotective Agents
Thyroid Hormones
Hormones
Prealbumin
Cytoskeleton
Neuroglia
Glutamic Acid
Brain
Thyronines
Sodium-Hydrogen Antiporter
Acidosis
Hypothermia
Reperfusion Injury
Blood-Brain Barrier
Actin Cytoskeleton
Thyroxine
Astrocytes
Endoplasmic Reticulum
Genes
Adenosine Triphosphatases

Keywords

  • Journal Article

Cite this

Molecular basis for certain neuroprotective effects of thyroid hormone. / Lin, Hung-Yun; Davis, Faith B; Luidens, Mary K; Mousa, Shaker A; Cao, James H; Zhou, Min; Davis, Paul J.

In: Frontiers in Molecular Neuroscience, Vol. 4, 2011, p. 29.

Research output: Contribution to journalReview article

Lin, Hung-Yun ; Davis, Faith B ; Luidens, Mary K ; Mousa, Shaker A ; Cao, James H ; Zhou, Min ; Davis, Paul J. / Molecular basis for certain neuroprotective effects of thyroid hormone. In: Frontiers in Molecular Neuroscience. 2011 ; Vol. 4. pp. 29.
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