ALS (Amyotrophic Lateral Sclerosis) tends to be called MND (Motor Neuron Disease) in the UK. It is also known as Lou Gehrig's disease because he was a famous baseball player whose career was ended when he died of ALS in his 30s. There are perhaps two main versions of ALS Familial (or inherited) and Sporadic which does not appear to be inherited. MND is perhaps a broader category which includes Progressive Muscular Atrophy (PMA), Primary Lateral Sclerosis (PLS) and Progressive Bulbar Palsy (PBP) as well as ALS. In this post I am going to concentrate on ALS. That is not to say that things I say in this post do not necessarily also apply to the other types of MND, but I have not looked at that question as yet. I wrote a post a few weeks ago What causes Parkinson's Disease - is it actually an accelerated form of brain aging? and since then have been doing some experimentation with a small number of biohackers who have Parkinsons Disease. The hypothesis is basically that th...
An interesting paper was published recently. Intracellular metabolic gradients dictate dependence on exogenous pyruvate This was from the same lab as the excellent paper A non-canonical tricarboxylic acid cycle underlies cellular identity . An interesting question that the paper answers is what drives the need for external pyruvate. The paper concludes "The requirement for pyruvate over lactate can be partially rescued by NAD+, suggesting that at least part of the role of pyruvate in development is regulation of cellular redox62. ". What I find particularly interesting about the link to NAD+ is that Complex 1 (which is reduced in stem cells) has a major role in maintaining NAD+ levels. Hence if it is to be inhibited in some form then something else needs to be done to maintain NAD+ levels. Although Complex 1 maintains mitochondrial NAD+ rather than cytosolic NAD+, depletion in the Mitochondria will block the Malate-Aspartate shuttle affecting the cytosol Pyruvate in th...