Research Topic

Targeting Thyroid Hormone-dependent Pathways in Proliferative and Degenerative Disorders

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Background: The treatment of disorders related to aberrant proliferation, differentiation, and renewal of cells and tissues is a new challenge that translational and clinical research are facing in these years. The spectrum of pathologies correlated with the alteration of such biological processes is ...

Background: The treatment of disorders related to aberrant proliferation, differentiation, and renewal of cells and tissues is a new challenge that translational and clinical research are facing in these years. The spectrum of pathologies correlated with the alteration of such biological processes is extremely wide and includes preneoplastic/neoplastic diseases, malformative and congenital disorders as well as degenerative diseases. Also, the number of organs and tissues affected by these disorders is very large and includes the nervous system, gut, liver, kidney and skin. Despite this heterogeneity, the crucial pathways involved in proliferation/differentiation and cell renewal are largely the same.

Recent findings indicate that thyroid hormones (THs) and their receptors (THRs) are implicated in the control of these pathways. As to aberrant proliferation, alteration of pathways related to intracellular THs has been already linked to carcinogenesis in the small and large bowel, skin and liver. On the other hand, a reduction in THRs signaling has been associated with neurodegenerative disorders, like Parkinson and Alzheimer disease. Moreover, defects in THs signaling cause alterations in cell differentiation leading to impaired organogenesis during fetal life.

The possibility to treat these diseases modulating the TH/THRs-related-pathway is intriguing. However, a strategy based on systemic administration of THs or anti-thyroidal drugs is not a suitable option in many cases, as systemic hyper- or hypothyroidism is associated with severe adverse effects. The harmful side effects of therapeutic supra-physiological concentrations of these hormones led researchers to investigate novel THs analogues devoid of cardiovascular and metabolic side effects. Currently, the identification and the possible use of new selective agonists of the beta isoform of THR is one of the most promising therapeutic approaches in the field of oncology and neurodegenerative disease. The development of novel alpha or beta selective thyromimetics and the characterization of new druggable targets in the THs/THRs pathway can lead to innovative therapeutic strategies based on molecular tuning of intracellular THs actions.

Details for the Authors: The goal of this Research Topic is to improve our knowledge on how the TH/THR axis influences the onset and progression of diseases related to altered proliferation/differentiation or of degenerative processes. A better understanding will hopefully lead to the identification of new targets and to the development of new drugs for precision medicine. Papers focusing on mechanisms by which the THs/THRs axis can influence cancer onset and progression, modulate cellular differentiation, affect degenerative diseases, in particular, neurodegenerative diseases are welcome. We are interested in both basic/translational research as well as clinical studies focusing on new drugs that modify the THs/THRs axis. While original research manuscripts and reviews are accepted, case reports are not within the scope of this Topic. The collection of experimental and clinical evidences displaying a link between THs/THRs dysregulation and pathological cell proliferation/differentiation or degeneration will shed light for the identification of new diagnostic and therapeutic targets for the treatment of a broad spectrum of human diseases.


Keywords: Thyroid hormones analogues, precision medicine, carcinogenesis, neurodegenerative diseases, tissue renewal and differentiation., THRs, THs


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