Mitochondrial medicine for neurodegenerative diseases

Abstract

Mitochondrial dysfunction has been reported in a wide array of neurological disorders ranging from neuromuscular to neurodegenerative diseases. Recent studies on neurodegenerative diseases have revealed that mitochondrial pathology is generally found in inherited or sporadic neurodegenerative diseases and is believed to be involved in the pathophysiological process of these diseases. Commonly seen types of mitochondrial dysfunction in neurodegenerative diseases include excessive free radical generation, lowered ATP production, mitochondrial permeability transition, mitochondrial DNA lesions, perturbed mitochondrial dynamics and apoptosis. Mitochondrial medicine as an emerging therapeutic strategy targeted to mitochondrial dysfunction in neurodegenerative diseases has been proven to be of value, though this area of research is still at in its early stage. In this article, we report on recent progress in the development of several mitochondrial therapies including antioxidants, blockade of mitochondrial permeability transition, and mitochondrial gene therapy as evidence that mitochondrial medicine has promise in the treatment of neurodegenerative diseases.

Fig. 1

Schematic figure of therapeutic strategies to protect mitochondria against neurodegeneration. In neurodegenerative diseases such as AD, PD, HD and ALS, mitochondria undergo increased ROS production, suppressed respiratory function, mtDNA lesions, mPTP formation, preapoptotic factors release and damaged dynamics/motility. These deleterious factors will eventually lead to neurodegeneration. Mitochondrial medicine, including oxidant scavenge, mPTP inhibition, mitochondrial gene therapy, anti-apoptosis and mitochondrial dynamics modulation, are promising therapeutic strategies to attenuate neurodegeneration and to halt the progression of neuronal injury in the neurodegenerative diseases.