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Thread: A novel explaination For ALS

  1. #1
    Join Date
    Jan 2008

    A novel explaination For ALS

    A friend sent this to me if anyone is interested.

    The lactate dyscrasia hypothesis of ALS
    What is interesting about many patients with ALS is that the function of the eye muscles is spared. Understanding what is different about the eye muscles compared to other muscles might therefore throw light on what is causing skeletal muscles to dysfunction. One noticeable characteristic of the ocular nerves and muscles is that they use lactic acid as a metabolic substrate to sustain function and therefore don't become fatigued by high lactic acid, unlike skeletal muscles. Thus, lactate is a metabolic substrate that sustains extraocular muscle function and prevents muscle fatigue suggesting that these muscles have high lactate turnover (i.e. the molecular machinery to convert lactate to pyruvate). Supporting this, lactate dehydrogenase (LDH) activity is detected in occulomotor neurons and in eye muscles. Alternatively, it is possible that lactate is also removed from the nerves/muscles via a lactate shuttle (muscle-neuronal lactate shuttle; MNLS), like the recently proposed astrocyte-neuronal lactate shuttle. We therefore propose that a MNLS exists to maintain lactate homeostasis between muscles and motoneurons (the neuromuscular unit) and that dysregulation of the MNLS results in lactate assimilation in the NMJ leading to cellular stress, toxicity and subsequent degeneration. The lack of neurotransmission would be expected to lead to muscular atrophy. Similarly, excess lactate accumulation in myocytes also may promote muscle degeneration, although it might be expected that peripheral motoneurons are more susceptible to high lactate levels than peripheral muscles. Progressive muscular atrophy (PMA) is another disease where dysregulation of lactate homeostasis could lead to motoneuron degeneration with subsequent rapid muscular atrophy.
    The loss of lactate homeostasis and subsequent death of motoneurons may create a vicious cycle whereby the remaining muscle fibers are required to work harder to compensate for normal muscle function, producing more lactate and/or other toxic radicals inducing further motor neurotoxicity that leads to further neuronal degeneration and death. This would explain the exponential progression of ALS leading to paralysis.

    Sivan Vadakkadath Meethala and Craig S. Atwood

    One thing I would like to mention is that they eye muscles are'nt affected, but the eye lid muscles can be. My brother can only lift the eyelid on one eye now, leaving the other one pretty useless.

  2. #2
    Senior Member
    Join Date
    Jan 2003
    Madison,Wisconsin, USA


    Hey, welcome to cc, Andes, good to see you posting. Debra

  3. #3
    Andes, the lactate dyscrasia hypothesis is indeed interesting. Actually, there are a couple of other muscles that ALS seems to spare. For example, the bladder, heart, intestinal, and vascular muscles are not so affected although the diaphragm and the sphincter muscles (being striated muscles) are susceptible. In contrast, muscular dystrophy affects heart and even bladder muscles.


  4. #4
    Good early source. Indeed an interesting article. What I think to understand from the article "Lactate dyscrasia: a novel explanation for amyotrophic lateral sclerosis" is that
    1) In the muscle: aspartate accumulates in the mitochondrion of the muscle cell, which leads finally to toxic levels of lactate at the neuromuscular junction.
    2) This leads to the inhibition of the conversion of oxaloacetate to aspartate. Because this conversion is coupled to the conversion of glutamate to alpha-ketoglutarate (by glutamate dehydrogenase), also glutamate will accumulate.

    My question is:
    - Could this also explain the success of a ketogenic diet in ALS? (because of its metabolic path)
    - What could help to lower the concentration of lactate at the site of the neuromuscular junction and to lower the concentration of glutamate at the synapse at the site of the motor neurons (next to Riluzole)?
    - Is ALS mainly caused by apoptosis of the mitochondria after which its cell will undergo apoptosis?
    - How comes that ALS is mostly a late onset disease?
    Last edited by fenice; 09-29-2010 at 04:16 PM.

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