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Cells
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Role of Thyroid Hormone in Neurodegenerative and Neurodevelopmental Disorders
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Role of Thyroid Hormone in Neurodegenerative and Neurodevelopmental Disorders

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cells of the Nervous System".

Deadline for manuscript submissions: 20 August 2025 | Viewed by 3667

Special Issue Editor

Dr. Janaína Sena de Souza

E-Mail Website
Guest Editor
Department of Pediatrics, University of California San Diego, San Diego, CA, USA
Interests: neurodegenerative and neurodevelopmental disorders; regenerative medicine; stem cells; brain organoids; neurons; astrocytes; neural progenitor cells; thyroid hormone; endocrine disruptors; complement system
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Thyroid hormones play a crucial role in the development and function of the central nervous system, with significant implications for both neurodevelopmental and neurodegenerative disorders. Disruptions in thyroid hormone signaling have been linked to a range of conditions, including cognitive impairments, mood disorders and neurodegenerative diseases such as Alzheimer’s and Parkinson’s. Recent advances in understanding the molecular and cellular mechanisms influenced by thyroid hormones offer new insights into their role in these disorders and open avenues for therapeutic interventions.

As an expert in the field with extensive experience in studying thyroid hormone effects on the brain, I am honored to serve as the editor of this Special Issue. My research has focused on the intersection of endocrinology and neuroscience, particularly on the impact of thyroid hormones on neurodevelopmental and neurodegenerative processes. I invite you to contribute your latest findings to this Special Issue, which aim to advance our understanding of the intricate relationships between thyroid hormones and brain health.

Dr. Janaína Sena de Souza
Guest Editor

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Keywords

  • thyroid hormones
  • neurodevelopmental and neurodegenerative disorders
  • central nervous system

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Published Papers (3 papers)

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Research

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21 pages, 3602 KiB  
Article
Novel Thyroid Hormone Receptor-β Agonist TG68 Exerts Anti-Inflammatory, Lipid-Lowering and Anxiolytic Effects in a High-Fat Diet (HFD) Mouse Model of Obesity
by Beatrice Polini, Caterina Ricardi, Francesca Di Lupo, Massimiliano Runfola, Andrea Bacci, Simona Rapposelli, Ranieri Bizzarri, Marco Scalese, Federica Saponaro and Grazia Chiellini
Cells 2025, 14(8), 580; https://doi.org/10.3390/cells14080580 - 11 Apr 2025
Viewed by 280
Abstract
Recent advances in drug development allowed for the identification of THRβ-selective thyromimetic TG68 as a very promising lipid lowering and anti-amyloid agent. In the current study, we first investigated the neuroprotective effects of TG68 on in vitro human models of neuroinflammation and β-amyloid [...] Read more.
Recent advances in drug development allowed for the identification of THRβ-selective thyromimetic TG68 as a very promising lipid lowering and anti-amyloid agent. In the current study, we first investigated the neuroprotective effects of TG68 on in vitro human models of neuroinflammation and β-amyloid neurotoxicity in order to expand our knowledge of the therapeutic potential of this novel thyromimetic. Subsequently, we examined metabolic and inflammatory profiles, along with cognitive changes, using a high-fat diet (HFD) mouse model of obesity. Our data demonstrated that TG68 was able to prevent either LPS/TNFα-induced inflammatory response or β-amyloid-induced cytotoxicity in human microglial (HMC3) cells. Next, we demonstrated that in HFD-fed mice, treatment with TG68 (10 mg/kg/day; 2 weeks) significantly reduced anxiety-like behavior in stretch–attend posture (SAP) tests while producing a 12% BW loss and a significant decrease in blood glucose and lipid levels. Notably, these data highlight a close relationship between improved serum metabolic parameters and a reduction of anxious behavior. Moreover, TG68 administration was observed to efficiently counteract HFD-altered central and peripheral expressions in mice with selected biomarkers of metabolic dysfunction, inflammation, and neurotoxicity, revealing promising neuroprotective effects. In conclusion, our work provides preliminary evidence that TG68 may represent a novel therapeutic opportunity for the treatment of interlinked diseases such as obesity and neurodegenerative diseases. Full article
(This article belongs to the Special Issue Role of Thyroid Hormone in Neurodegenerative and Neurodevelopmental Disorders)
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Review

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19 pages, 1541 KiB  
Review
Thyroid Hormones and Brain Development: A Focus on the Role of Mitochondria as Regulators of Developmental Time
by Filip Vujovic and Ramin M Farahani
Cells 2025, 14(3), 150; https://doi.org/10.3390/cells14030150 - 21 Jan 2025
Viewed by 1544
Abstract
Thyroid hormones (THs) regulate metabolism in a homeostatic state in an adult organism. During the prenatal period, prior to the establishment of homeostatic mechanisms, THs assume additional functions as key regulators of brain development. Here, we focus on reviewing the role of THs [...] Read more.
Thyroid hormones (THs) regulate metabolism in a homeostatic state in an adult organism. During the prenatal period, prior to the establishment of homeostatic mechanisms, THs assume additional functions as key regulators of brain development. Here, we focus on reviewing the role of THs in orchestrating cellular dynamics in a developing brain. The evidence from the reviewed scientific literature suggests that the developmental roles of the hormones are predominantly mediated by non-genomic mitochondrial effects of THs due to attenuation of genomic effects of THs that antagonise non-genomic impacts. We argue that the key function of TH signalling during brain development is to orchestrate the tempo of self-organisation of neural progenitor cells. Further, evidence is provided that major neurodevelopmental consequences of hypothyroidism stem from an altered tempo of cellular self-organisation. Full article
(This article belongs to the Special Issue Role of Thyroid Hormone in Neurodegenerative and Neurodevelopmental Disorders)
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Other

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11 pages, 2221 KiB  
Perspective
Role of Thyroid Hormone in Neurodegenerative Disorders of Older People
by Arshag D. Mooradian and Michael J. Haas
Cells 2025, 14(2), 140; https://doi.org/10.3390/cells14020140 - 18 Jan 2025
Viewed by 1116
Abstract
Thyroid dysfunction is associated with a number of neuropsychiatric manifestations. Cognitive decline is a common feature of hypothyroidism and clinical or subclinical hyperthyroidism. In addition, there is a significant association between thyroid hormone (TH) levels and the degree of cognitive impairment in Parkinson’s [...] Read more.
Thyroid dysfunction is associated with a number of neuropsychiatric manifestations. Cognitive decline is a common feature of hypothyroidism and clinical or subclinical hyperthyroidism. In addition, there is a significant association between thyroid hormone (TH) levels and the degree of cognitive impairment in Parkinson’s disease (PD). The pathophysiology of TH-related neurodegeneration include changes in the blood–brain barrier, increased cellular stress, altered processing of β-amyloid precursor protein and the effect of TH on neuronal cell viability. The neurotoxicity of TH is partially mediated by the thyroid hormone responsive protein (THRP). This protein is 83% homologous to mouse c-Abl-interacting protein-2 (Abi2), a c-Abl-modulating protein with tumor suppressor activity. In cell cultures, increasing THRP expression either with TH treatment or exogenously through transfecting neuronal or PC 12 cells causes cell necrosis. The expression of exogenous THRP in other cells such as the colonic epithelial cell line Caco-2 and the glial cell line U251 has no effect on cell viability. The effect of THRP on cell viability is not modulated by c-Abl tyrosine kinase. The causal relationship between specific biochemical perturbations in cerebral tissue and thyroid dysfunction remains to be elucidated. Full article
(This article belongs to the Special Issue Role of Thyroid Hormone in Neurodegenerative and Neurodevelopmental Disorders)
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