Molecular Basis for Certain Neuroprotective Effects of Thyroid Hormone

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 (T3) and l-thyroxine (T4), 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 [Ca2+]i.c. by activation of plasma membrane Ca2+–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 T4 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 T4 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.

Transthyretin Is a Key Regulator of Myoblast Differentiation

“…TTR , which is known as a carrier protein for thyroxin and retinol binding protein, has been shown to play a critical role in homeostasis of the nervous system [34]. We previously identified TTR as one of the genes highly up-regulated in different depots of bovine muscle tissue during myogenesis [30].…”

Thyroid Hormones Enhance Mitochondrial Function in Human Epidermis

“…However, given that genomic TH actions are mediated by TH nuclear receptors, c-erb Aα and Aβ (Tata, 2013;Verga Falzacappa et al, 2009;Weitzel and Iwen, 2011), it is relevant that human keratinocytes express both TH nuclear receptors (Billoni et al, 2000;Contreras-Jurado et al, 2011). Intriguingly, isoforms of the two receptors, like p43, have also been found in mitochondria ( Cioffi et al, 2013;Lin et al, 2011;Tata, 2013;Weitzel et al, 2003). Thus, it is conceivable that these isoforms could mediate some direct, non-genomic effects of THs on human keratinocyte mitochondria.…”

Pharmacological hypothermia: a potential for future stroke therapy?

“…The role of thyronamines, which are thyroid hormone derivatives whose side chains have been decarboxylated, 100 has been explored in several experiments pertaining to neuroprotection, although only one study thus far has evaluated their significance with respect to hypothermia and ischemic stroke injury. 101 The completely deiodinated thyronamine compound (T0AM) and another thyroxine derivative that retains the 3-iodine, 3-iodothyronamine (T1AM), were injected intraperitoneally into mice 1 h after MCAO at a dose of 50 mg/kg.…”