Innovative Target Therapies Are Able to Block the Inflammation Associated with Dysfunction of the Cholesterol Biosynthesis Pathway

International Journal of Molecular Sciences

Annalisa Marcuzzi²  Elisa Piscianz⁴  Claudia Loganes²  Liza Vecchi Brumatti⁴  Alessandra Knowles⁴  Sabrine Bilel³  Alberto Tommasini⁴  Roberta Bortul²  Marina Zweyer²  Ge Zhang¹ 

[1] Department of Medicine, Surgery and Health Sciences, University of Trieste, Piazzale Europa 1, Trieste 34128, ItalyDepartment of Medicine, Surgery and Health Sciences, University of Trieste, Piazzale Europa 1, Trieste 34128, Italy;Cluster in Biomedicine (CBM scrl), Trieste 34128, Italy;Institute for Maternal and Child Health—IRCCS “Burlo Garofolo”, via dell’Istria, 65/1, Trieste 34137, Italy;

关键词: cholesterol;    mitochondria;    apoptosis;    autophagy;    inflammasome;   

DOI  :  10.3390/ijms17010047

来源: mdpi

【 摘 要 】

The cholesterol pathway is an essential biochemical process aimed at the synthesis of bioactive molecules involved in multiple crucial cellular functions. The end products of this pathway are sterols, such as cholesterol, which are essential components of cell membranes, precursors of steroid hormones, bile acids and other molecules such as ubiquinone. Several diseases are caused by defects in this metabolic pathway: the most severe forms of which cause neurological involvement (psychomotor retardation and cerebellar ataxia) as a result of a variety of cellular impairments, including mitochondrial dysfunction. These pathologies are induced by convergent mechanisms in which the mitochondrial unit plays a pivotal role contributing to defective apoptosis, autophagy and mitophagy processes. Unraveling these mechanisms would contribute to the development of effective drug treatments for these disorders. In addition, the development of biochemical models could have a substantial impact on the understanding of the mechanism of action of drugs that act on this pathway in multifactor disorders. In this review we will focus in particular on inhibitors of cholesterol synthesis, mitochondria-targeted drugs and inhibitors of the inflammasome.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.