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Review
. 2025 Nov;62(11):14883-14922.
doi: 10.1007/s12035-025-05058-2. Epub 2025 May 23.

The Intricate Relationship of Trk Receptors in Brain Diseases and Disorders

Sarthak Dahiya  1 , Poonam Sharma  2   3 , Bhupesh Sharma  4 , Priyanka Saroj  1 , Harsha Kharkwal  5 , Nitin Sharma  6
Affiliations
Review

The Intricate Relationship of Trk Receptors in Brain Diseases and Disorders

Sarthak Dahiya et al. Mol Neurobiol. 2025 Nov.

Abstract

The tropomyosin-related tyrosine kinases or neurotrophic tyrosine kinase receptors are a group of tyrosine kinases that play a crucial role in regulating neuronal growth and development. Neurotrophins are a class of protein-secreting cells that serve as the primary ligand for the Trk receptors. The four primary neurotrophins are nerve growth factor (NGF), brain-derived nerve factor (BDNF), neurotrophin-3, and neurotrophin-4/5. Mounting evidence suggests that Trk receptors can be categorized into three types: TrkA, TrkB, and TrkC. These receptors play a crucial role in facilitating neuronal growth and development. Trk receptors influence the survival and differentiation of neurons via many signalling cascades. Neurotrophin interaction with Trk receptors triggers a signalling cascade involving PLC, PI3K/Akt, and Ras/MAPK signalling pathways. Emerging evidence suggests that diminished neurotrophic support, changes in Trk receptor expression, or disruptions in signalling cascades play a crucial role in the development of various neurological disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), autism spectrum disorder (ASD), and many more. This review specifically explores therapeutic approaches targeting Trk receptors, their ligands, and Trk signaling in the context of various brain disorders. We focus on the potential for modulating or inhibiting Trk receptors as a treatment strategy for brain diseases.

Keywords: Alzheimer’s disease; Autism; Neurotrophins; Parkinson’s disease; Trk; Trk signalling.

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Conflict of interest statement

Declarations. Competing interests: The authors declare no competing interests. Clinical Trial Number: Not applicable.

References

    1. Accogli A, Addour-Boudrahem N, Srour M (2020) Neurogenesis, neuronal migration, and axon guidance. Handb Clin Neurol 173:25–42. https://doi.org/10.1016/B978-0-444-64150-2.00004-6 - DOI - PubMed
    1. Fornaro M, Giovannelli A, Foggetti A, Muratori L, Geuna S, Novajra G, Perroteau I (2020) Role of neurotrophic factors in enhancing linear axonal growth of ganglionic sensory neurons in vitro. Neural Regenerat Res 15(9):1732–1739. https://doi.org/10.4103/1673-5374.276338 - DOI
    1. Moya-Alvarado G, Tiburcio-Felix R, Ibáñez MR, Aguirre-Soto AA, Guerra MV, Wu C, Mobley WC, Perlson E et al (2023) BDNF/TrkB signaling endosomes in axons coordinate CREB/mTOR activation and protein synthesis in the cell body to induce dendritic growth in cortical neurons. Elife 12:e77455. https://doi.org/10.7554/eLife.77455 - DOI - PubMed - PMC
    1. Puehringer D, Orel N, Lüningschrör P, Subramanian N, Herrmann T, Chao MV, Sendtner M (2013) EGF transactivation of Trk receptors regulates the migration of newborn cortical neurons. Nat Neurosci 16(4):407–415 - DOI - PubMed - PMC
    1. Paredes MF, James D, Gil-Perotin S, Kim H, Cotter JA, Ng C, Sandoval K, Rowitch DH et al (2016) Extensive migration of young neurons into the infant human frontal lobe. Science 354(6308):aaf7073. https://doi.org/10.1126/science.aaf7073 - DOI - PubMed - PMC

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