Anavex Life Sciences Corp (AVXL)

[falconer66a]

Binary? Or multifactorial?

Could there be a case where over expression of S1R function is as detrimental as "under-expression"?

The real issue is what, exactly, is sigma-1 receptor activation, agonism, or “expression.”

It appears to be an error to presume that sigma-1 receptor activation is binary; on or off, or at some point within that binary gradient. Simply, this protein modulates or facilitates a number of diverse, unconnected cellular processes. Multifactorial instead of binary.

Moreover, activation can be either positive or negative. Blarcamesine’s activation of the protein causes or allows it to favorably modulate downstream reactions and processes. Other sigma-1 receptor activators do the opposite. Like blarcamesine, they bind to the protein (are ligands), but they disrupt normal downstream cellular processes.

More specifically, about “over expression” of the sigma-1 receptor protein (meaning, lots of it is synthesized, “expressed” from its controlling genetics on its gene; this is a genetic phenomenon. Gene expression. In most cases, there are homeostatic processes that turn off gene expression when the genetic product, in this case the sigma-1 receptor protein, reaches a desired level.

What would happen, then, if too much sigma-1 receptor protein were synthesized? One problem would be where the excess protein would reside in the cell. Normally, it resides at the endoplasmic reticulum, where it modulates protein folding, etc. But where would excess sigma-1 proteins go? Would they have any activity in the cell? Or, would lysosomes take them up as cellular excesses or wastes and digest them? This would be a normal homeostatic process.