Pharmacological advances in mitochondrial therapy

Abstract

Mitochondria play a vital role in cellular metabolism and are central mediator of intracellular signalling, cell differentiation, morphogenesis and demise. An increasingly higher number of pathologies is linked with mitochondrial dysfunction, which can arise from either genetic defects affecting core mitochondrial components or malfunctioning pathways impairing mitochondrial homeostasis. As such, mitochondria are considered an important target in several pathologies spanning from neoplastic to neurodegenerative diseases as well as metabolic syndromes. In this review we provide an overview of the state-of-the-art in mitochondrial pharmacology, focusing on the novel compounds that have been generated in the bid to correct mitochondrial aberrations. Our work aims to serve the scientific community working on translational medical science by highlighting the most promising pharmacological approaches to target mitochondrial dysfunction in disease.

Mitochondrial Function and Parkinson’s Disease: From the Perspective of the Electron Transport Chain

“…So far there is still no silver bullet to prevent or to ameliorate PD progression. Non-etheless, new compounds or existing drugs await testing as potential therapeutic strategies for PD via improving ETC functions ( Singh et al, 2021 ).…”

Targeting Mitochondria in Diabetes

“…Taking into account all studies mentioned above, mitochondria appear to be a valuable target for the development of novel drugs with a potential for a more integrative therapeutic approach, treating IR at different levels and in different tissues. The most promising pharmacological approaches to target mitochondria in different pathologies were recently reviewed [ 109 ]. Here we focus on mitochondrial targeting agents that might be relevant in therapy of diabetes and insulin resistance ( Figure 2 ).…”

Mitochondria in Neurogenesis: Implications for Mitochondrial Diseases

“…Although in the past 30 years mitochondrial medicine has made enormous progresses in understanding the genetic and biochemical pathomechanisms of mitochondrial disorders, 87,88 current treatments still remain focused on controlling complications and reducing the symptoms 89,90 . The lack of effective therapies for most mitochondrial diseases is due to several problems, including a specific lack of effective preclinical models for performing drug discovery 91 .…”

“…The interpretation that the neuronal pathology of mitochondrial diseases is caused by neurodegeneration influenced treatment schemes centered on antioxidants to prevent the buildup of damaging ROS 87 . However, antioxidants, which may dampen physiological ROS signaling, 103 failed to consistently improve the patient symptomatology 88,90 . Conversely, gene augmentation therapy based on the expression of a healthy copy of SURF1 in patient NPCs improved early neuronal morphogenesis 98 .…”