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.
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].
old, this is the disease to which the late Ara Parshegian lost several grandchildren. He set up a foundation to fight it.
Also, Investor noted Orphazyme A/S as a company (located in Denmark) that has a drug to address NPC, but was turned down by fda, even though results indicated success in treatment.
Full disclosure: It was a meme stock for a few days before fda turn down. Went from 4-5 to 77 ... I sold at 37 as it was climbing.