Table 2.
Studies of the action of thyroid hormone and thyroid hormone analogs targeting the brain
| Condition | Compound | TR isoform selectivity | Model | Results | Reference |
|---|---|---|---|---|---|
| Alzheimer’s disease | T3 | THRB = THRA | Hypothyroid mIce and neural cell culture | T3 treatment downregulates beta amyloid precursor protein expression | (Contreras-Jurado & Pascual, 2012; O’Barr, et al., 2006) |
| AHDS (Mct8 mutation) | DITPA | THRB = THRA | Mouse model of MCT8 deficiency | Restore neuronal differentiation and brain function in mice | (Di Cosmo, et al., 2009) |
| AHDS (Mct8 mutation) | Tetrac | THRB>THRA (2-fold to 3-fold) | Mouse model of MCT8 deficiency | Restore neuronal differentiation and brain function in mice | (Horn, et al., 2013) |
| AHDS (Mct8 mutation) | DITPA | THRB = THRA | Humans with AHDS | Reduced serum T3, reduced hypermetabolism, no impact on neurologic manifestations | (Verge, et al., 2012) |
| X-linked adrenal-leukodystrophy (X-ALD) | Sobetirome (also referred to as GC1) | THRB>THRA (10-fold) | Mouse model of X-ALD and fibroblasts from X-ALD patients | Stimulation of ABCD2 expression, reduced very long chain fatty acid deposition in adrenals and some reduction in brain, Induction of ABCD2 in fibroblasts of X-ALD patients | (Hartley, et al., 2017; Milanesi & Brent, 2017) |
| Traumatic Brain Injury | T4 | THRB = THRA | Mouse hippocampal brain slice injury model | Promotes neurotrophins and neuronal survival | (Shulga, et al., 2009) |
| Traumatic Brain Injury | T3 | THRB = THRA | Mouse model of TBI, T3 treatment 1 hour after injury | Reduced brain edema, improved cognitive and motor function compared to control | (Crupi, et al., 2013) |
| Traumatic Brain Injury | T4 | THRB = THRA | CCI model in rat, T4 treatment 1 hour after injury | Reduced brain edema, restoration of some T3-responsive genes in the brain | (Li, et al., 2017) |
| Stroke | T3 | THRB = THRA | MCA occlusion mouse model, T3 before or after occlusion | Attenuation of ischemia and edema | (Sadana, et al., 2015) |
| Stoke | Thyronamine (3-T1AM) | Actions not mediated by THR | Given 1 hour after stroke in mouse model | Hypothermia, marked reduction in ischemic damage | (Doyle, et al., 2007) |
ADHD-Allan-Herndon-Dudley Syndrome, CCI-controlled cortical injury, THRA-thyroid hormone receptor alpha, THRB-thyroid hormone receptor beta, MCA-middle cerebral artery,