RESUMO
The impact of mitochondrial dysfunction on the pathogenesis of cardiovascular disease is increasing. However, the precise underlying mechanism remains unclear. Mitochondria produce cellular energy through oxidative phosphorylation while regulating calcium homeostasis, cellular respiration, and the production of biosynthetic chemicals. Nevertheless, problems related to cardiac energy metabolism, defective mitochondrial proteins, mitophagy, and structural changes in mitochondrial membranes can cause cardiovascular diseases via mitochondrial dysfunction. Mitofilin is a critical inner mitochondrial membrane protein that maintains cristae structure and facilitates protein transport while linking the inner mitochondrial membrane, outer mitochondrial membrane, and mitochondrial DNA transcription. Researchers believe that mitofilin may be a therapeutic target for treating cardiovascular diseases, particularly cardiac mitochondrial dysfunctions. In this review, we highlight current findings regarding the role of mitofilin in the pathogenesis of cardiovascular diseases and potential therapeutic compounds targeting mitofilin.
Assuntos
Doenças Cardiovasculares , Proteínas Mitocondriais , Proteínas Musculares , Humanos , Animais , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/tratamento farmacológico , Proteínas Musculares/metabolismo , Proteínas Musculares/genética , Proteínas Mitocondriais/metabolismo , Mitocôndrias Cardíacas/metabolismo , Mitocôndrias Cardíacas/efeitos dos fármacosRESUMO
Based on ninety three acetylcholinesterase inhibitors (AChEIs) which have the same mechanism of action but are different in structural characteristics, the pharmacophore model for acetylcholinesterase inhibitor was constructed by the CATALYST system. The optimal pharmacophore model with three hydrophobic units, a ring aromatic unit and a hydrogen-bond acceptor unit were confirmed (Weight = 3.29, RMS = 0.53, total cost-null cost = 62.75, Correl = 0.93, Config = 19.05). This pharmacophore model will act on the double active site of acetylcholinesterase and is able to predict the activity of known acetylcholinesterase inhibitors that are used for clinical treatment of Alzheimer's disease (AD), and can be further used to identify structurally diverse compounds that have higher activity treating with Alzheimer's disease (AD) by virtual screening.