Monocarboxylate Transporter 8 Deficiency: Delayed or Permanent Hypomyelination?

Vancamp, Pieter; Demeneix, Barbara; Remaud, Sylvie

doi:10.3389/fendo.2020.00283

Cited by 30 publications

(37 citation statements)

References 163 publications

(223 reference statements)

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“…1 ). For an overview of the main mechanisms of disease, the reader is referred to recent reviews [ 2 , 10 , 11 ]. This review will focus on important clinical characteristics of MCT8 deficiency and provides an overview of treatment options available and under development.…”

Section: Clinical Characteristics Of Mct8 Deficiencymentioning

confidence: 99%

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Monocarboxylate transporter 8 deficiency: update on clinical characteristics and treatment

2021

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Defective thyroid hormone transport due to deficiency in thyroid hormone transporter monocarboxylate transporter 8 (MCT8) results in severe neurodevelopmental delay due to cerebral hypothyroidism and in clinical negative sequelae following a chronic thyrotoxic state in peripheral tissues. The life expectancy of patients with MCT8 deficiency is severely impaired. Increased mortality is associated with lack of head control and being underweight at young age. Treatment options are available to alleviate the thyrotoxic state; particularly, treatment with the thyroid hormone analogue triiodothyroacetic acid seems a promising therapy. This review provides an overview of key clinical features and treatment options available and under development for this rare disorder.

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Section: Clinical Characteristics Of Mct8 Deficiencymentioning

confidence: 99%

“…In magnetic resonance imaging of patients with MCT8 deficiency, delayed myelination and abnormal cerebral white matter volume are key findings [ 10 , 12 , 17 ].…”

Section: Clinical Characteristics Of Mct8 Deficiencymentioning

confidence: 99%

Monocarboxylate transporter 8 deficiency: update on clinical characteristics and treatment

2021

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“…LAT1 transports several TH metabolites in the order 3,3’-T2>T3~rT3>T4. The presence of multiple membrane transporters appears particularly relevant in Allan-Herndon-Dudley Syndrome (AHDS), where decreased numbers of oligodendrocytes in the brain correlates with TH due to mutation of the MCT8 and contributes to the pathology ( 19 ). As OATP1C1 is not highly expressed in the pre- and perinatal human brain, MCT10, LAT1 and LAT2 are the most likely candidates for the basal TH supply in these patients.…”

Section: Blood Transport Metabolisation Cellular Uptake and Cellular mentioning

confidence: 99%

Physiological Role and Use of Thyroid Hormone Metabolites - Potential Utility in COVID-19 Patients

Frőhlich

Wahl

2021

Front. Endocrinol.

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Thyroxine and triiodothyronine (T3) are classical thyroid hormones and with relatively well-understood actions. In contrast, the physiological role of thyroid hormone metabolites, also circulating in the blood, is less well characterized. These molecules, namely, reverse triiodothyronine, 3,5-diiodothyronine, 3-iodothyronamine, tetraiodoacetic acid and triiodoacetic acid, mediate both agonistic (thyromimetic) and antagonistic actions additional to the effects of the classical thyroid hormones. Here, we provide an overview of the main factors influencing thyroid hormone action, and then go on to describe the main effects of the metabolites and their potential use in medicine. One section addresses thyroid hormone levels in corona virus disease 19 (COVID-19). It appears that i) the more potently-acting molecules T3 and triiodoacetic acid have shorter half-lives than the less potent antagonists 3-iodothyronamine and tetraiodoacetic acid; ii) reverse T3 and 3,5-diiodothyronine may serve as indicators for metabolic dysregulation and disease, and iii) Nanotetrac may be a promising candidate for treating cancer, and resmetirom and VK2809 for steatohepatitis. Further, the use of L-T3 in the treatment of severely ill COVID-19 patients is critically discussed.

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“…Thyroid hormone is a key endocrine signal conserved in all vertebrates, including humans, regulating many homeostatic processes such as growth, reproduction and energy metabolism. TH also regulates CNS development ( Gothié et al, 2017 ) by influencing all neurodevelopmental processes, including cell cycle progression, fate choice, migration, differentiation, axo- and synaptogenesis, and myelination ( Zoeller and Rovet, 2004 ; Moog et al, 2017 ; Krieger et al, 2019 ; Vancamp et al, 2020 ). Under pathophysiological conditions, TH acts on each of these processes, promoting regeneration in the adult fish brain that retained large numbers of NSCs ( Grandel et al, 2006 ; Bhumika and Darras, 2014 ).…”

Section: The Potential Of Thyroid Hormone As a Pro-repair Cuementioning

confidence: 99%

Thyroid Hormone and Neural Stem Cells: Repair Potential Following Brain and Spinal Cord Injury

Vancamp¹,

Butruille²,

Demeneix³

et al. 2020

Front. Neurosci.

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Neurodegenerative diseases are characterized by chronic neuronal and/or glial cell loss, while traumatic injury is often accompanied by the acute loss of both. Multipotent neural stem cells (NSCs) in the adult mammalian brain spontaneously proliferate, forming neuronal and glial progenitors that migrate toward lesion sites upon injury. However, they fail to replace neurons and glial cells due to molecular inhibition and the lack of pro-regenerative cues. A major challenge in regenerative biology therefore is to unveil signaling pathways that could override molecular brakes and boost endogenous repair. In physiological conditions, thyroid hormone (TH) acts on NSC commitment in the subventricular zone, and the subgranular zone, the two largest NSC niches in mammals, including humans. Here, we discuss whether TH could have beneficial actions in various pathological contexts too, by evaluating recent data obtained in mammalian models of multiple sclerosis (MS; loss of oligodendroglial cells), Alzheimer's disease (loss of neuronal cells), stroke and spinal cord injury (neuroglial cell loss). So far, TH has shown promising effects as a stimulator of remyelination in MS models, while its role in NSC-mediated repair in other diseases remains elusive. Disentangling the spatiotemporal aspects of the injury-driven repair response as well as the molecular and cellular mechanisms by which TH acts, could unveil new ways to further exploit its proregenerative potential, while TH (ant)agonists with cell type-specific action could provide safer and more target-directed approaches that translate easier to clinical settings.

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Monocarboxylate Transporter 8 Deficiency: Delayed or Permanent Hypomyelination?

Cited by 30 publications

References 163 publications

Monocarboxylate transporter 8 deficiency: update on clinical characteristics and treatment

Monocarboxylate transporter 8 deficiency: update on clinical characteristics and treatment

Physiological Role and Use of Thyroid Hormone Metabolites - Potential Utility in COVID-19 Patients

Thyroid Hormone and Neural Stem Cells: Repair Potential Following Brain and Spinal Cord Injury

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