Oxidative stress and mitochondrial damage: importance in non-SOD1 ALS.
Carrì MT1, Valle C2, Bozzo F1, Cozzolino M3. 1Department of Biology, Università di Roma Tor Vergata Rome, Italy ; Fondazione Santa Lucia, IRCCS Rome, Italy. 2Fondazione Santa Lucia, IRCCS Rome, Italy ; Institute of Cell Biology and Neurobiology, IBCN, National Research Council, CNR Rome, Italy. 3Institute of Translational Pharmacology, National Research Council, CNR, Molecular Mechanisms of Neurodegenerative Diseases Rome, Italy.
It is well known that mitochondrial damage (MD) is both the major contributor to oxidative stress (OS) (the condition arising from unbalance between production and removal of reactive oxygen species) and one of the major consequences of OS, because of the high dependance of mitochondrial function on redox-sensitive targets such as intact membranes. Conditions in which neuronal cells are not able to cope with MD and OS seem to lead or contribute to several neurodegenerative diseases including Amyotrophic Lateral Sclerosis (ALS), at least in the most studied superoxide dismutase 1 (SOD1)-linked genetic variant. As summarized in this review, new evidence indicates that MD and OS play a role also in non-SOD1 ALS and thus they may represent a target for therapy despite previous failures in clinical trials.