Modulation of mitochondrial dysfunction for treatment of disease

Modulation of mitochondrial dysfunction for treatment of disease Bioorganic & Medicinal Chemistry Letters 29 (2019) 1270–1277 Contents lists available at ScienceDirect Bioorganic & Medicinal Chemistry Letters journal homepage: www.elsevier.com/locate/bmcl Digest Michael Webb , Dionisia P. Sideris, Margaret Biddle Mitobridge Inc, an Astellas Company, 1030 Massachusetts Ave, Cambridge, MA 02138, USA ARTICLE INFO ABSTRACT Keywords: Mitochondrial dysfunction is a causative and/or exacerbating feature of many pathologies. We discuss below Mitochondria approaches to modulate mitochondrial dysfunction that involve (1) increasing their energetic efficiency by Energetics targeting gene expression regulators such as PPAR or AMPK, (2) using antioxidant compounds to reduce the Dynamics toxic reactive oxygen species mitochondria produce under stress, or (3) modulating aspects on the innate mi- ROS tochondrial quality control system. The latter comprise linked processes of biogenesis, dynamic morphological Biogenesis changes, and elimination of defective mitochondria by mitophagy. We discuss representative compounds in all three classes. Introduction tRNAs, and two ribosomal RNAs, are directly causative of a number of disorders, many with a neurological presentation. However, mi- Mitochondria are cellular organelles bounded by a double mem- tochondrial dysfunction, manifesting as defects in ATP synthesis and brane that are found within almost all mammalian cells. The inner increased generation of toxic reactive oxygen and nitrogen species, is http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Bioorganic & Medicinal Chemistry Letters Elsevier

Modulation of mitochondrial dysfunction for treatment of disease

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Publisher
Elsevier
Copyright
Copyright © 2019 The Authors
ISSN
0960-894x
D.O.I.
10.1016/j.bmcl.2019.03.041
Publisher site
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Abstract

Bioorganic & Medicinal Chemistry Letters 29 (2019) 1270–1277 Contents lists available at ScienceDirect Bioorganic & Medicinal Chemistry Letters journal homepage: www.elsevier.com/locate/bmcl Digest Michael Webb , Dionisia P. Sideris, Margaret Biddle Mitobridge Inc, an Astellas Company, 1030 Massachusetts Ave, Cambridge, MA 02138, USA ARTICLE INFO ABSTRACT Keywords: Mitochondrial dysfunction is a causative and/or exacerbating feature of many pathologies. We discuss below Mitochondria approaches to modulate mitochondrial dysfunction that involve (1) increasing their energetic efficiency by Energetics targeting gene expression regulators such as PPAR or AMPK, (2) using antioxidant compounds to reduce the Dynamics toxic reactive oxygen species mitochondria produce under stress, or (3) modulating aspects on the innate mi- ROS tochondrial quality control system. The latter comprise linked processes of biogenesis, dynamic morphological Biogenesis changes, and elimination of defective mitochondria by mitophagy. We discuss representative compounds in all three classes. Introduction tRNAs, and two ribosomal RNAs, are directly causative of a number of disorders, many with a neurological presentation. However, mi- Mitochondria are cellular organelles bounded by a double mem- tochondrial dysfunction, manifesting as defects in ATP synthesis and brane that are found within almost all mammalian cells. The inner increased generation of toxic reactive oxygen and nitrogen species, is

Journal

Bioorganic & Medicinal Chemistry LettersElsevier

Published: Jun 1, 2019

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