Activation of neurotrophin signalling with light‑inducible receptor tyrosine kinases

Zhang, Wei; Shu, Zhao; Lu, Linjie; Fan, Zhimin; Ye, Shixin

doi:10.3892/mmr.2022.12586

Cited by 3 publications

(1 citation statement)

References 37 publications

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“…Recently, several groups have developed optobiological methods to control the activation of TrkA and other related receptor tyrosine kinases (RTK) in a reversible and spatially selective manner using light. − Our lab reported an improved light-induced dimer (iLiD) based system for activating RTKs in a temporally controlled manner and showed that the TrkA version of the tool, opto-iTrkA, which uses blue light to activate the intracellular kinase domain of TrkA (iTrkA), was capable of activating downstream signaling pathways in cell line models . In this work, we demonstrate that the opto-iTrkA system is suitable for light-inducible activation of TrkA in a primary neuron culture and in mice.…”

Section: Introductionmentioning

confidence: 99%

Light-Inducible Activation of TrkA for Probing Chronic Pain in Mice

Liu,

Mohr,

Hope

et al. 2024

ACS Chem. Biol.

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Chronic pain is a prevalent problem that plagues modern society, and better understanding its mechanisms is critical for developing effective therapeutics. Nerve growth factor (NGF) and its primary receptor, Tropomyosin receptor kinase A (TrkA), are known to be potent mediators of chronic pain, but there is a lack of established methods for precisely perturbing the NGF/TrkA signaling pathway in the study of pain and nociception. Optobiological tools that leverage light-induced protein−protein interactions allow for precise spatial and temporal control of receptor signaling. Previously, our lab reported a blue lightactivated version of TrkA generated using light-induced dimerization of the intracellular TrkA domain, opto-iTrkA. In this work, we show that opto-iTrkA activation is able to activate endogenous ERK and Akt signaling pathways and causes the retrograde transduction of phospho-ERK signals in dorsal root ganglion (DRG) neurons. Opto-iTrkA activation also sensitizes the transient receptor potential vanilloid 1 (TRPV1) channel in cellular models, further corroborating the physiological relevance of the optobiological stimulus. Finally, we show that opto-iTrkA enables lightinducible potentiation of mechanical sensitization in mice. Light illumination enables nontraumatic and reversible (<2 days) sensitization of mechanical pain in mice transduced with opto-iTrkA, which provides a platform for dissecting TrkA pathways for nociception in vitro and in vivo.

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Section: Introductionmentioning

confidence: 99%

Light-Inducible Activation of TrkA for Probing Chronic Pain in Mice

Liu,

Mohr,

Hope

et al. 2024

ACS Chem. Biol.

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Research progress of PROTACs for neurodegenerative diseases therapy

Cai,

Yang,

et al. 2024

Bioorganic Chemistry

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Receptor Tyrosine Kinase Signaling Involves Echinococcus–Host Intercommunication: A Potential Therapeutic Target in Hepatic Echinococcosis

Gao,

Bianba,

et al. 2024

TropicalMed

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Echinococcosis, one of the most serious and life-threatening parasitic forms of zoonosis worldwide, is caused by the larvae of Echinococcus granulosus (E. granulosus) and Echinococcus multilocularis (E. multilocularis). Various drugs are being applied clinically to treat zoonosis; however, their therapeutic efficacy remains a great challenge, especially with albendazole as the preferred drug of choice. Receptor tyrosine kinase (RTK) signaling controls normal cellular proliferation, differentiation, and metabolism in humans and mammals, which are intermediate hosts of E. granulosus and E. multilocularis. Disruption of RTK signaling can cause various forms of carcinogenesis and exacerbate the progression of certain forms of parasitic disease. As a result, a significant number of studies on tyrosine kinase inhibitors (TKIs) have been conducted for the treatment of cancer and parasitic infection, with some TKIs already approved for clinical use for cancer. Notably, RTK signaling has been identified in the parasites E. granulosus and E. multilocularis; however, the mechanisms of RTK signaling response in Echinococcus–host intercommunication are not fully understood. Thus, understanding the RTK signaling response in Echinococcus–host intercommunication and the potential effect of RTK signaling is crucial for identifying new drug targets for echinococcosis. The present review illustrates that RTK signaling in the host is over-activated following infection by E. granulosus or E. multilocularis and can further facilitate the development of metacestodes in vitro. In addition, some TKIs exert strong parasitostatic effects on E. granulosus or E. multilocularis, both in vitro and/or in vivo, through downregulation of RTK signaling molecules. The summarized findings suggest that RTK signaling may be a promising drug target and that TKIs could be potential anti-Echinococcus drugs warranting further research.

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Activation of neurotrophin signalling with light‑inducible receptor tyrosine kinases

Cited by 3 publications

References 37 publications

Light-Inducible Activation of TrkA for Probing Chronic Pain in Mice

Light-Inducible Activation of TrkA for Probing Chronic Pain in Mice

Research progress of PROTACs for neurodegenerative diseases therapy

Receptor Tyrosine Kinase Signaling Involves Echinococcus–Host Intercommunication: A Potential Therapeutic Target in Hepatic Echinococcosis

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