Receptor Tyrosine Kinases as Therapeutic Targets for Alcohol Use Disorder.
Kana HamadaAmy W LasekPublished in: Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics (2021)
The receptor tyrosine kinases (RTKs) are a large family of proteins that transduce extracellular signals to the inside of the cell to ultimately affect important cellular functions such as cell proliferation, survival, apoptosis, differentiation, and migration. They are expressed in the nervous system and can regulate behavior through modulation of neuronal and glial function. As a result, RTKs are implicated in neurodegenerative and psychiatric disorders such as depression and addiction. Evidence has emerged that 5 RTKs (tropomyosin-related kinase B (TrkB), RET proto-oncogene (RET), anaplastic lymphoma kinase (ALK), fibroblast growth factor receptor (FGFR), and epidermal growth factor receptor (EGFR)) modulate alcohol drinking and other behaviors related to alcohol addiction. RTKs are considered highly "druggable" targets and small-molecule inhibitors of RTKs have been developed for the treatment of various conditions, particularly cancer. These kinases are therefore attractive targets for the development of new pharmacotherapies to treat alcohol use disorder (AUD). This review will examine the preclinical evidence describing TrkB, RET, ALK, FGFR, and EGFR modulation of alcohol drinking and other behaviors relevant to alcohol abuse.
Keyphrases
- epidermal growth factor receptor
- alcohol use disorder
- tyrosine kinase
- advanced non small cell lung cancer
- alcohol consumption
- small molecule
- cell proliferation
- small cell lung cancer
- cell therapy
- oxidative stress
- single cell
- squamous cell carcinoma
- stem cells
- protein kinase
- diffuse large b cell lymphoma
- papillary thyroid
- spinal cord
- mesenchymal stem cells
- neuropathic pain
- signaling pathway
- pi k akt
- intimate partner violence