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Review
. 2024 Aug 16:3:1458038.
doi: 10.3389/frdem.2024.1458038. eCollection 2024.

Tyrosine kinases: multifaceted receptors at the intersection of several neurodegenerative disease-associated processes

Max Stevenson  1 , Norah K Algarzae  2 , Charbel Moussa  1
Affiliations
Review

Tyrosine kinases: multifaceted receptors at the intersection of several neurodegenerative disease-associated processes

Max Stevenson et al. Front Dement. .

Abstract

Tyrosine kinases (TKs) are catalytic enzymes activated by auto-phosphorylation that function by phosphorylating tyrosine residues on downstream substrates. Tyrosine kinase inhibitors (TKIs) have been heavily exploited as cancer therapeutics, primarily due to their role in autophagy, blood vessel remodeling and inflammation. This suggests tyrosine kinase inhibition as an appealing therapeutic target for exploiting convergent mechanisms across several neurodegenerative disease (NDD) pathologies. The overlapping mechanisms of action between neurodegeneration and cancer suggest that TKIs may play a pivotal role in attenuating neurodegenerative processes, including degradation of misfolded or toxic proteins, reduction of inflammation and prevention of fibrotic events of blood vessels in the brain. In this review, we will discuss the distinct roles that select TKs have been shown to play in various disease-associated processes, as well as identify TKs that have been explored as targets for therapeutic intervention and associated pharmacological agents being investigated as treatments for NDDs.

Keywords: autophagy; blood vessels; c-KIT; inflammation; neurodegenerative diseases; tyrosine kinase.

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Conflict of interest statement

CM is an inventor on several US and international Georgetown University patents to use BK40143 and BK40197 and other tyrosine kinase inhibitors as a treatment for neurodegenerative diseases. Georgetown University spun out the technology (April 2020) to a start-up company, KeifeRx, in which it holds equity and for which CM is a co-founder, shareholder, and consultant. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Proposed mechanisms for how tyrosine kinase signaling may contribute to neurodegenerative disease pathology. Tyrosine kinase signaling has been demonstrated to promote several processes associated with neurodegenerative diseases, including impaired autophagic clearance of neurotoxic protein aggregates, increased neuroinflammation, increased vascular fibrosis and permeability, and dysregulated neurotransmitter levels.
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References

    1. Ali D. W., Salter M. W. (2001). NMDA receptor regulation by Src kinase signalling in excitatory synaptic transmission and plasticity. Curr. Opin. Neurobiol. 11, 336–342. 10.1016/S0959-4388(00)00216-6 - DOI - PubMed
    1. Ali S., Mansour A. G., Huang W., Queen N. J., Mo X., Anderson J. M., et al. . (2020). CSF1R inhibitor PLX5622 and environmental enrichment additively improve metabolic outcomes in middle-aged female mice. Aging 12, 2101–2122. 10.18632/aging.102724 - DOI - PMC - PubMed
    1. Alvarez A. R., Sandoval P. C., Leal N. R., Castro P. U., Kosik K. S. (2004). Activation of the neuronal c-Abl tyrosine kinase by amyloid-β-peptide and reactive oxygen species. Neurobiol. Dis. 17, 326–336. 10.1016/j.nbd.2004.06.007 - DOI - PubMed
    1. Anderson K. E., Stevenson M., Varghese R., Hebron M. L., Koppel E., McCartin M., et al. . (2022). Alteration of autophagy and glial activity in nilotinib-treated Huntington's disease patients. Metabolites 12:1225. 10.3390/metabo12121225 - DOI - PMC - PubMed
    1. Arsenault S., Benoit R. Y., Clift F., Moore C. S. (2022). Does the use of the Bruton Tyrosine Kinase inhibitors and the c-kit inhibitor masitinib result in clinically significant outcomes among patients with various forms of multiple sclerosis? Mult. Scler. Relat. Disord. 67:104164. 10.1016/j.msard.2022.104164 - DOI - PubMed

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