Targeting mitochondrial impairment for the treatment of cardiovascular diseases: from hypertension to ischemia reperfusion injury, searching for new pharmacological targets
| Autor: | Todisco, Simona, Musio, Biagia, Pesce, Vito, Cavalluzzi, Maria Maddalena, Petrosillo, Giuseppe, La Piana, Gianluigi, Sgobba, Maria Noemi, Schlosserová, Nikola, Cafferati Beltrame, Lucas, Di Lorenzo, Rosa, Tragni, Vincenzo, Marzulli, Domenico, Guerra, Lorenzo, De Grassi, Anna, Gallo, Vito, Volpicella, Mariateresa, Palese, Luigi Leonardo, Lentini, Giovanni, Pierri, Ciro Leonardo |
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| Rok vydání: | 2022 |
| Předmět: |
Pharmacology
Drug-Repurposing Mitochondrial permeability transition pore Molecular modeling of mitochondrial proteins Mitochondrial pyruvate carrier Aquaporin Cardiolipin Cardiovascular diseases Genomics Hypertension Ischemia reperfusion injury Metabolomics Mitochondrial carriers Mitochondrial diseases Mitochondrial dynamics Mitochondrial dysfunction Mitochondrial impairment Mitochondrial metabolite transport system Mitochondrial pharmacological targets Mitochondrial targets for CVD treatments Respiratory chain Transcriptomics Voltage-dependent anion channels Biochemistry |
| Zdroj: | Biochemical pharmacology. |
| ISSN: | 1873-2968 |
| Popis: | Mitochondria and mitochondrial proteins represent a group of promising pharmacological-target candidates in the search of new molecular targets and drugs to counteract the onset of hypertension and more in general cardiovascular diseases (CVDs). Indeed, several mitochondrial pathways result impaired in CVDs, showing ATP depletion and ROS production as common traits of cardiac tissue degeneration. Thus, targeting mitochondrial dysfunction in cardiomyocytes can represent a successful strategy to prevent heart failure. In this context, the identification of new pharmacological targets among mitochondrial proteins paves the way for the design of new selective drugs. Thanks to the advances in omics approaches, to a greater availability of mitochondrial crystallized protein structures and to the development of new computational approaches for protein 3D-modelling and drug-design, it is now possible to investigate in detail impaired mitochondrial pathways in CVDs. Furthermore, it is possible to design new powerful drugs able to hit the selected pharmacological targets in a highly selective way to rescue mitochondrial dysfunction and prevent cardiac tissue degeneration. The role of mitochondrial dysfunction in the onset of CVDs appears increasingly evident, as reflected by the impairment of proteins involved in lipid peroxidation, mitochondrial dynamics, respiratory chain complexes, and membrane polarization maintenance in CVD patients. Conversely, little is known about proteins responsible for the cross-talk between mitochondria and cytoplasm in cardiomyocytes. Mitochondrial transporters of the SLC25A family, in particular, are responsible for the translocation of nucleotides (e.g., ATP), amino acids (e.g., aspartate, glutamate, ornithine), organic acids (e.g. malate and 2-oxoglutarate), and other cofactors (e.g., inorganic phosphate, NAD |
| Databáze: | OpenAIRE |
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