Anavex Life Sciences Corp (AVXL)

[amstocks82]

The answer given by MycroftHolmes matches most published sources:

"...the Sigma Receptor does not impact protein folding directly by chaperoning but rather indirectly but modulating PERK, IRE1a, and ATF6 and thus the UPR (Unfolded Protein Response) ..."

OFP's quote: "If you recall, one of the main chaperone functions of S1R is correct protein folding."

That comment is still not correct. It is not a "chaperone function".

Why is this important? The "protein chaperone" topic is a very complex and large topic.
https://www.researchgate.net/publication/51508608_Molecular_chaperones_in_protein_folding_and_proteostasis

The comment that, "...one of the main chaperone functions of S1R is correct protein folding." implies incorrectly that the sigma-1 receptor is a protein chaperone. It is not. The sigma-1 receptor is a "receptor chaperone". Something totally different.

"The sigma-1 receptor is a receptor chaperone whose activity can be activated/deactivated by specific ligands. Under physiological conditions, the sigma-1 receptor chaperones the functional IP3 receptor at the endoplasmic reticulum and mitochondrion interface to ensure proper Ca(2+) signaling from endoplasmic reticulum into mitochondrion. However, under pathological conditions whereby cells encounter enormous stress that results in the endoplasmic reticulum losing its global Ca(2+) homeostasis, the sigma-1 receptor translocates and counteracts the arising apoptosis. Thus, the sigma-1 receptor is a receptor chaperone essential for the metabotropic receptor signaling and for the survival against cellular stress."

Or:

"Communication between the endoplasmic reticulum (ER) and mitochondrion is important for bioenergetics and cellular survival. The ER supplies Ca(2+) directly to mitochondria via inositol 1,4,5-trisphosphate receptors (IP3Rs) at close contacts between the two organelles referred to as mitochondrion-associated ER membrane (MAM). We found here that the ER protein sigma-1 receptor (Sig-1R), which is implicated in neuroprotection, carcinogenesis, and neuroplasticity, is a Ca(2+)-sensitive and ligand-operated receptor chaperone at MAM. Normally, Sig-1Rs form a complex at MAM with another chaperone, BiP. Upon ER Ca(2+) depletion or via ligand stimulation, Sig-1Rs dissociate from BiP, leading to a prolonged Ca(2+) signaling into mitochondria via IP3Rs. Sig-1Rs can translocate under chronic ER stress. Increasing Sig-1Rs in cells counteracts ER stress response, whereas decreasing them enhances apoptosis. These results reveal that the orchestrated ER chaperone machinery at MAM, by sensing ER Ca(2+) concentrations, regulates ER-mitochondrial interorganellar Ca(2+) signaling and cell survival. "

https://www.researchgate.net/publication/5865783_Sigma-1_Receptor_Chaperones_at_the_ER-_Mitochondrion_Interface_Regulate_Ca2_Signaling_and_Cell_Survival