Targeting mitochondria: The road to mitochondriotropic antioxidants and beyond

• Type: Chapter or Part of a Book
• Date: 2018

Authors

Fernanda Borges (Author) FCUP

Book

Title: Mitochondrial biology and experimental therapeutics

Pages: 333-358

ISBN: 978-3-319-73344-9

Publisher: Springer Publishing

Indexing

Scopus - 6 Citations

Other information

Authenticus ID: P-00N-XHC

DOI: 10.1007/978-3-319-73344-9_16

Abstract (EN): Mitochondria are sub-cellular organelles that play a central role in energy metabolism, being these organelles currently recognized as one important target for new drug discovery programs addressed to find innovative therapeutic solutions for diverse pathologic events, such as cancer, cardiovascular, and neurological diseases. Although attractive, the success of the strategies developed so far has been hampered by several challenges and limitations, and until now the Food and Drug Administration (FDA) has not approved a drug for mitochondrial therapy. Currently, the most effective strategy to deliver drugs specifically to mitochondria is the covalent link of a lipophilic cation, namely triphenylphosphonium (TPP), to a pharmacophore of interest. Within this framework two mitochondriotropic antioxidants (MitoQ and SkQ1) have entered in human clinical trials as a therapeutic solution for oxidativestress related diseases. In this chapter, the efforts done so far to target small-molecule antioxidants to mitochondria as potential therapeutics or diagnostic tools have been reviewed. Although TPP cation has been the most extensively used mitochondrial- targeting cation, there are still controversies surrounding this approach, namely related with its intrinsic toxicity. Consequently, efforts must be done in finding new cation carriers, and to guarantee that the cargo does indeed access the mitochondrial matrix and does not merely associate with the mitochondrial membranes. Moreover, in vivo biodistribution, pharmacokinetics and long- term toxic effects studies to provide accurate information about efficacy and toxicity are still an emergent issue to make available the translation from bench to bedside. © Springer International Publishing AG, part of Springer Nature 2018.

Language: English

Type (Professor's evaluation): Scientific