Anavex Life Sciences Corp (AVXL)

[georgejjl]

The structure and role of S2R
S2R is an under-researched 18- to 21-kDa protein having four transmembrane domains with N and C terminals extending to the cytoplasm [3]. This receptor forms an integral component of the endoplasmic reticulum membrane known as transmembrane protein 97 (TMEM97), and also referred to as meningioma-associated protein (MAC30). TMEM97 plays roles in cholesterol homeostasis and sterol transport in Niemann-Pick disease type C1. It also participates in the regulation of the intracellular concentration of calcium ions

Sigma 2 receptor may be a target for the treatment of Niemann-Pick disease type C1.

https://link.springer.com/article/10.1007/s43440-021-00310-7

The s2 receptor was finally identified as TMEM97 in 2017 [86]. This was determined via a an affinity chromatography approach in which a s2-specific ligand fixed to a column was used to isolate candidate proteins from calf liver [86]. Candidates were identified by mass spectrometry and screened through heterologous expression and pharmacological profiling [86]. Expression of TMEM97 in cells lacking s2 receptor confers a s2 receptor binding profile to those cells, and siRNA knockdown of TMEM97 proportionally reduces s2 binding [86], confirming that TMEM97 and the s2 receptor are one and the same.

TMEM97/s2 receptor biology and therapeutic potential

Currently, little is known about TMEM97 except that it resides in the endoplasmic reticulum and lysosomes [91], where it may bind to cholesterol [91] and regulate the Niemann-Pick protein NPC1 [92].

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6748033/#!po=0.649351

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