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The Two-Pore Channel 2 in Human Physiology and Diseases: Functional Characterisation and Pharmacology
Laura Lagostena1, Velia Minicozzi2, Martina Meucci3
1Institute of Biophysics, National Research Council, Via De Marini 6, 16149 Genova, Italy.
Abstract:
Two-pore channel 2 (TPC2) is a member of the endolysosomal ion channel family, playing critical roles in intracellular calcium signaling and endomembrane dynamics. This review provides an in-depth analysis of TPC2, covering its structural and functional properties, physiological roles, and involvement in human diseases. We discuss current experimental approaches to studying TPC2, including heterologous expression in plant vacuoles and computational modeling strategies. Particular emphasis is placed on the structural determinants of ion permeation, with a focus on the selectivity filter and the central cavity's influence on channel kinetics. Furthermore, we explore emerging roles of TPC2 in viral infections, particularly SARS-CoV-2, and in cancer, including melanoma progression and neoangiogenesis. The inhibitory potential of natural compounds, such as naringenin, is also examined. By offering a comprehensive overview of current knowledge and methodologies, this review underscores the potential of TPC2 as a promising pharmacological target in both infectious and neoplastic diseases.
Insights
Two-pore channel 2 (TPC2) is an endolysosomal ion channel crucial for cell signaling and disease. This review details TPC2
Area of Science:
- Molecular Biology
- Cell Biology
- Pharmacology
Background:
- Two-pore channel 2 (TPC2) is an endolysosomal ion channel.
- It plays key roles in intracellular calcium signaling and endomembrane dynamics.
- Dysregulation of TPC2 is implicated in various human diseases.
Purpose of the Study:
- To provide an in-depth analysis of TPC2's structure, function, and physiological roles.
- To explore TPC2's involvement in human diseases, including viral infections and cancer.
- To review current methodologies for studying TPC2 and its potential as a drug target.
Main Methods:
- Review of existing literature on TPC2.
- Analysis of structural determinants of ion permeation.
- Examination of experimental approaches like heterologous expression and computational modeling.
Main Results:
- TPC2's structure, including the selectivity filter and central cavity, influences channel kinetics.
- Emerging roles of TPC2 in SARS-CoV-2 infection, melanoma, and neoangiogenesis are highlighted.
- Natural compounds like naringenin show inhibitory potential against TPC2.
Conclusions:
- TPC2 is a critical regulator of cellular processes with significant implications in disease.
- Understanding TPC2's structure-function relationship is key to developing targeted therapies.
- TPC2 represents a promising pharmacological target for infectious and neoplastic diseases.
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