But, protein folding is even more complex.
Nice, educational video on protein folding. Good intro; but incomplete.
It's claimed or implied that protein folding is solely dependent upon the particular sequence of amino acids in the protein. Doubtless, this a major, even requisite pre-condition. If the wrong amino acids get inserted or substituted, the protein will fold improperly. This is the mechanism of most mutations; a genetics, amino acid sequence problem.
But, in regard to blarcamesine (the Anavex drug) treating various central nervous system (CNS) diseases, which involve or are caused by mis-folded proteins (in most cases, reaction-controlling enzymes), the proteins (enzymes) don't mis-fold because of new genetic, amino acid sequence errors. The genes controlling protein synthesis in people with Alzheimer's disease are the same in childhood as in old age. No Alzheimer's in childhood; but the disease appears with age. Same genes, but waste-clearing proteins abundant in childhood are no longer produced. With age, the enzyme proteins that clear wastes in the neuron mis-fold, or fail to fold altogether. Normally-cleared metabolic wastes accumulate; neuron functions become ever more compromised.
The video failed to tell where protein folding occurs. Most of it happens in, is directed by the mitochondria. Chemical conditions in those organelles have to be just-so. Exactly the proper pH, with sufficient adenosine triphosphate (ATP) to provide the energy driving the folding reactions. Various minerals, particularly calcium ions, also have to be present and available in precise concentrations, at precise locations. If any of these protein folding factors are anomalous, the protein, an essential reaction-controlling enzyme, gets literally bent out of shape, and is thereby unable to catalyze its waste-clearing reactions. Wastes accumulate, one of the CNS diseases sets in.
In the neuron, blarcamesine, propitiously, binds to the sigma-1 receptor protein and causes it to function properly and effectively. Among other things, that restores the required, proper chemistry inside the attached mitochondria. Properly-shaped proteins can then, as in youth, be folded. Wastes, once again, can be cleared.
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