Saturday, 21 September 2013

Anti-Oxidants for Neuroprotection

KATP Channel Opener Diazoxide Prevents Neurodegeneration: A New Mechanism of Action via Antioxidative Pathway Activation.Virgili N, Mancera P, Wappenhans B, Sorrosal G, Biber K, Pugliese M, Espinosa-Parrilla JF. PLoS One. 2013 Sep 11;8(9):e75189. doi: 10.1371/journal.pone.0075189.

Pharmacological modulation of ATP-sensitive potassium channels has become a promising new therapeutic approach for the treatment of neurodegenerative diseases due to their role in mitochondrial and cellular protection. For instance, diazoxide, a well-known ATP-sensitive potassium channel activator with high affinity for mitochondrial component of the channel has been proved to be effective in animal models for different diseases. 

Here, we analyzed the ability of diazoxide for protecting neurons front different neurotoxic insults in vitro and ex vivo. Results showed that diazoxide effectively protects NSC-34 motoneurons from glutamatergic, oxidative and inflammatory damage. Moreover, diazoxide decreased neuronal death in organotypic hippocampal slice cultures after exicitotoxicity and preserved myelin sheath in organotypic cerebellar cultures exposed to pro-inflammatory demyelinating damage. In addition, we demonstrated that one of the mechanisms of actions implied in the neuroprotective role of diazoxide is mediated by the activation of Nrf2 expression and nuclear translocation. Nrf2 expression was increased in NSC-34 neurons in vitro as well as in the spinal cord of experimental autoimmune encephalomyelitis animals orally administered with diazoxide. Thus, diazoxide is a neuroprotective agent against oxidative stress-induced damage and cellular dysfunction that can be beneficial for diseases such as multiple sclerosis.

I don't normally do these types of post because it is just science fiction at the moment. Diazoxide can do many things including including blocking production of insulin and causing vasodilation and so could drop blood pressure, so whilst it may protect nerves it would have other unwanted effects. However,of interest this study suggests that the neuroprotective effect could be mediated by Nrf2. This is a potential target for BG-12 (Tecfidera),so will it be neuroprotective,maybe, but does it get in the brain to do this job? 


2 comments:

  1. How do these potassium channels differ from the ones that Ampyra targets?

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    Replies
    1. I believe they are the same. Ampyra is a very large molecule (4-Aminopyridyne) which wraps around the axons attaching to potassium channels. I'd think this medication should be taken before Ampyra/4-AP
      or after 6 hours past. May it increase chances of seizures ? needs to be tested.

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