Soy Protein Blocks Calpain Cell Damage

HD Lighthouse Contributing Editor's Comment: In October of 2002 Huntington's disease(HD) researcher Marcy McDonald and colleagues published the results of a clever experiment.

They took a few wild(researcher talk for normal) mice and a few genetic HD mice and gave them all identical head whacks. The brains of the HD mice were just as tough as the wild mice brains.

When the researchers examined all the little brains they came to a conclusion that did not totally support much of then current research. Caspase activation and apoptosis (programmed cell death) has little to do with HD. The smoking gun was an enzyme called calpain.(1)

Calpain might catabolize (break down) brain cells as it is known to catabolize muscle cells. Calpain causes muscle damage in intensely exercising athletes. Soy protein is a calpain blocker known to decrease muscle damage in rats.(2)

Soy protein is available in soy milk and other soy stuff at you local food store .

The following abstract is more evidence that calpain is the smoking gun in HD progression. --Jerry
Posted to the HDL: 02 Jul 2003

Calpain is a major cell death effector in selective striatal degeneration induced in vivo by 3-nitropropionate : implications for Huntington's disease.

Striatal cell death in Huntington's Disease (HD) may involve mitochondrial defects, NMDA[neurotransmitter]-mediated excitotoxicity, and activation of death effector proteases such as caspases and calpain.

However, the precise contribution of mitochondrial defects in the activation of these proteases in HD is unknown. Here, we addressed this question by studying the mechanism of striatal cell death in rat models of HD using the mitochondrial complex II inhibitor 3-nitropropionic acid (3-NP).

The neurotoxin was either given by intraperitoneal injections (acute model) or over 5 d by constant systemic infusion using osmotic pumps (chronic model) to produce either transient or sustained mitochondrial deficits. Caspase-9 activation preceded neurodegeneration in both cases. However, caspase-8 and caspase-3 were activated in the acute model, but not in the chronic model, showing that 3-NP does not require activation of these caspases to produce striatal degeneration.

In contrast, activation of calpain was specifically detected in the striatum in both models and this was associated with a calpain-dependent cleavage of huntingtin. Finally, in the chronic model, which mimics a steady blockade of complex II activity reminiscent of HD, selective calpain inhibition prevented the abnormal calpain-dependent processing of huntingtin, reduced the size of the striatal lesions, and almost completely abolished the 3-NP-induced DNA fragmentation in striatal cells.

The present results demonstrate that calpain is a predominant effector of striatal cell death associated with mitochondrial defects in vivo.This suggests that calpain may play an important role in HD pathogenesis and could be a potential therapeutic target to slow disease progression.

Source: Adopted from: HDL, J Neurosci. 2003 Jun 15;23(12):5020-30 Bizat N, et al.

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