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Unraveling the Potential of EphA4: A Breakthrough Target and Beacon of Hope for Neurological Diseases

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Abstract

Erythropoietin-producing hepatocellular carcinoma A4 (EphA4) is a transmembrane receptor protein which is a part of the most prominent family of receptor tyrosine kinases (RTKs). It serves a crucial role in both physiological, biological, and functional states binding with their ligand like Ephrins. Its abundance in the majority of the body's systems has been reported. Moreover, it draws much attention in the CNS since it influences axonal and vascular guidance. Also, it has a widespread role at the pathological state of various CNS disorders. Reports suggest it obstructs axonal regeneration in various neurodegenerative diseases and neurological disorders. Although, neuro-regeneration is still an open challenge to the modern drug discovery community.  Hence, in this review, we will provide information about the role of EphA4 in neurological diseases by which it may emerge as a therapeutic target for CNS disease. We will also provide a glance at numerous signaling pathways that activate or inhibit the EphA4-associated biological processes contributing to the course of neurodegenerative diseases. Thus, this work might serve as a basis for futuristic studies that are related to the target-based drug discovery in the field of neuro-regeneration.

Graphical Abstract

Pathological and physiological events associated with EphA4 and Ephrin upregulation and interaction.

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Acknowledgements

Meenal Verma and Manjeet Chopra received the scholarship from the Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Govt. of India. Color illustrations were prepared using the paid version of Biorender.com.

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The authors did not receive support from any organization for the submitted work.

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MV contributed in the literature search and drafting of the manuscript. MC contributed the outline and editing of the manuscript. HK did the concept design and finalized the manuscript.

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Correspondence to Hemant Kumar.

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Verma, M., Chopra, M. & Kumar, H. Unraveling the Potential of EphA4: A Breakthrough Target and Beacon of Hope for Neurological Diseases. Cell Mol Neurobiol 43, 3375–3391 (2023). https://doi.org/10.1007/s10571-023-01390-0

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  • DOI: https://doi.org/10.1007/s10571-023-01390-0

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