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Review

RET Receptor Tyrosine Kinase: Role in Neurodegeneration, Obesity, and Cancer

Institute of Biotechnology, University of Helsinki, HiLIFE, Viikinkaari 5D, 00014 Helsinki, Finland
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Int. J. Mol. Sci. 2020, 21(19), 7108; https://doi.org/10.3390/ijms21197108
Received: 20 August 2020 / Revised: 23 September 2020 / Accepted: 24 September 2020 / Published: 26 September 2020
(This article belongs to the Special Issue Kinase Signal Transduction 2.0)
Rearranged during transfection (RET) is the tyrosine kinase receptor that under normal circumstances interacts with ligand at the cell surface and mediates various essential roles in a variety of cellular processes such as proliferation, differentiation, survival, migration, and metabolism. RET plays a pivotal role in the development of both peripheral and central nervous systems. RET is expressed from early stages of embryogenesis and remains expressed throughout all life stages. Mutations either activating or inhibiting RET result in several aggressive diseases, namely cancer and Hirschsprung disease. However, the physiological ligand-dependent activation of RET receptor is important for the survival and maintenance of several neuronal populations, appetite, and weight gain control, thus providing an opportunity for the development of disease-modifying therapeutics against neurodegeneration and obesity. In this review, we describe the structure of RET, its signaling, and its role in both normal conditions as well as in several disorders. We highlight the differences in the signaling and outcomes of constitutive and ligand-induced RET activation. Finally, we review the data on recently developed small molecular weight RET agonists and their potential for the treatment of various diseases. View Full-Text
Keywords: rearranged in transfection (RET); neurodegeneration; obesity; cancer; RET agonist; neurorestoration; retinitis pigmentosa; hirschsprung disease; glial cell line-derived neurotrophic factor (GDNF) family ligands (GFLs); growth differentiation factor 15 (GDF15) rearranged in transfection (RET); neurodegeneration; obesity; cancer; RET agonist; neurorestoration; retinitis pigmentosa; hirschsprung disease; glial cell line-derived neurotrophic factor (GDNF) family ligands (GFLs); growth differentiation factor 15 (GDF15)
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MDPI and ACS Style

Mahato, A.K.; Sidorova, Y.A. RET Receptor Tyrosine Kinase: Role in Neurodegeneration, Obesity, and Cancer. Int. J. Mol. Sci. 2020, 21, 7108. https://doi.org/10.3390/ijms21197108

AMA Style

Mahato AK, Sidorova YA. RET Receptor Tyrosine Kinase: Role in Neurodegeneration, Obesity, and Cancer. International Journal of Molecular Sciences. 2020; 21(19):7108. https://doi.org/10.3390/ijms21197108

Chicago/Turabian Style

Mahato, Arun Kumar, and Yulia A. Sidorova. 2020. "RET Receptor Tyrosine Kinase: Role in Neurodegeneration, Obesity, and Cancer" International Journal of Molecular Sciences 21, no. 19: 7108. https://doi.org/10.3390/ijms21197108

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