Department Of Pharmacology

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Author: search.filters.author.Randhawa, Puneet Kaur

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    Insights into receptor tyrosine kinases signaling in neurodegenerative disorders: opportunities and translational perspectives
    (Elsevier, 2023-07-06T00:00:00) Randhawa, Puneet Kaur; Jaggi, Amteshwar Singh; Bali, Anjana
    Receptor tyrosine kinases (RTKs) are a group of membrane-bound receptors comprising of extracellular ligand-binding domain, a transmembrane domain, and an intracellular catalytic domain. RTKs play a crucial role in various cellular processes including cellular growth, motility, cell differentiation, and cell metabolism. The dysregulation of RTK activity is a contributing factor in the progression of many neurodegenerative disorders. Studies revealed the alterations rearranged during transfection, epidermal growth factor receptor 1, vascular endothelial growth factor-B TAM receptors, and tropomyosin receptor kinase in neurodegenerative disorders. Further, PI3K/Akt/GSK-3? and Wnt/catenin signaling pathways are found to be major pathways for neuronal survival and neurite outgrowth induced by RTKs. This chapter summarizes the most important aspects of RTK subfamilies and their intraneuronal signaling mechanisms in different neurodegenerative disorders. The understanding of the fundamental mechanisms of RTKs in neurodegenerative disorders has important implications for the selection of a suitable neuroprotective agent. � 2023 Elsevier Inc. All rights reserved.
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    A focus on Rho/ROCK signaling pathway: An emerging therapeutic target in depression
    (Elsevier B.V., 2023-03-08T00:00:00) Hanifa, Mohd; Singh, Mohini; Randhawa, Puneet Kaur; Jaggi, Amteshwar Singh; Bali, Anjana
    Depression is the most common mental health disorder worldwide; however, the exact cellular and molecular mechanisms of this major depressive disorder are unclear so far. Experimental studies have demonstrated that depression is associated with significant cognitive impairment, dendrite spine loss, and reduction in connectivity among neurons that contribute to symptoms associated with mood disorders. Rho/Rho-associated coiled-coil containing protein kinase (ROCK) receptors are exclusively expressed in the brain and Rho/ROCK signaling has gained considerable attention as it plays a crucial role in the development of neuronal architecture and structural plasticity. Chronic stress-induced activation of the Rho/ROCK signaling pathway promotes neuronal apoptosis and loss of neural processes and synapses. Interestingly, accumulated evidence has identified Rho/ROCK signaling pathways as a putative target for treating neurological disorders. Furthermore, inhibition of the Rho/ROCK signaling pathway has proven to be effective in different models of depression, which signify the potential benefits of clinical Rho/ROCK inhibition. The ROCK inhibitors extensively modulate antidepressant-related pathways which significantly control the synthesis of proteins, and neuron survival and ultimately led to the enhancement of synaptogenesis, connectivity, and improvement in behavior. Therefore, the present review refines the prevailing contribution of this signaling pathway in depression and highlighted preclinical shreds of evidence for employing ROCK inhibitors as disease-modifying targets along with possible underlying mechanisms in stress-associated depression. � 2023 Elsevier B.V.