It is well known that we cannot live without Mn superoxide dismutase (MnSOD), and cannot stay healthy without the Cu,Zn members (Cu,ZnSOD) of the family of superoxide dismutases. Such knowledge has inspired the development of several classes of SOD mimics. Since the start of the era of SOD mimics over 30 years ago, our knowledge of the chemistry and biochemistry of those compounds and of the redox biology of the cell has greatly increased.

In turn, it has become obvious that rather than acting as SOD mimics, these compounds are able to undergo diverse reactions within the redox-rich cellular milieu, serving more as gatekeepers of healthy cellular physiological environments rather than acting as specific SOD mimics. In turn, we more correctly and frequently identify them as redox-active therapeutics. Two of those compounds are now in five Phase II clinical trials. For the first time, drugs whose actions originate from targeting the cellular redox environment are in clinical development - representing a breakthrough in drug development - as opposed to conventional drugs that prevalently target specific proteins.

The aim of this Special Issue is to collect manuscripts on SOD enzymes and redox-active drugs that (i) heal diseased cells and tissues by suppressing oxidative stress, primarily via restoring the physiological redox environment of a cell, impacting the components of redox-based signaling pathways and (ii) suppress tumor growth. Many of those compounds are either solely mimicking SOD enzymes or indirectly upregulating those enzymes. We invite the submission of manuscripts that address the therapeutic effects and mechanistic studies on redox-active therapeutics as well as on SOD enzymes. Studies on SOD knockout- or overexpressor cells or animals are welcome, to contribute to our understanding of the role of these enzymes in cellular signaling and maintenance of the physiological redox environment. We welcome both original research and review articles.

We would like to dedicate our Special Issue to a great colleague, dear friend, and exceptional scientist – Margaret Tome - who greatly influenced how we presently understand the in vivo mechanism of action of Mn porphyrin-based SOD mimics.

Potential topics include but are not limited to the following:

• Superoxide dismutase enzymes (SOD) in health and disease
• SOD mimics in health and disease
• Knock-out and SOD over-expressor mice
• Redox-active therapeutics in treating oxidative stress
• Role of metal complexes in oxidative stress
• Use of nitrones/nitroxides in mitigating oxidative stress
• Clinical trials on the use of redox-active therapeutics in cancer, radiation injury and in injuries of normal tissues, such as organ ischemia/reperfusion, skin infections, or organ transplants
• Proteomic and redox proteomics of diseases affected by oxidative stress and therapies aimed to treat them