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. 2020 Aug 10;16(1):106–107. doi: 10.4103/1673-5374.286961

Figure 1.

Figure 1

Putative neuroprotective functions of Sigma-1 receptor in motor neurons.

In motor neurons Sigma-1 receptor (S1R) is enriched at the vicinity of presynaptic cholinergic C-terminals and interacts with potassium channels, Kv2.1 and SK, to fine-tune neuronal excitability. S1R is also a main resident of mitochondrial associated endoplasmic reticulum (ER) membranes where it modulates calcium transfer from ER to mitochondria through inositol triphosphate receptor (IP3R). As a consequence, this boosts nicotinamide adenine dinucleotide cofactor (NADH) levels through the tricarboxylic acid cycle (TCA), which is indispensable for ATP production by oxidative phosphorylation (OXPHOS). S1R also facilitates cholesterol escort from ER to mitochondria by interaction with steroidogenic acute regulatory protein (StAR) and voltage dependent anion channel (VDAC). During a cellular stress or when S1R is activated, S1R dissociates from 78 kDa glucose-regulated protein (GRP78) and stabilizes inositol requiring enzyme 1 (IRE1) dimers. Dimerization of IRE1 leads to the expression of active spliced X-box binding protein 1 (XBP1), a transcription factor that induces ER stress response. When activated, S1R can also translocate to the nucleus on Emerin and regulates transcriptional activity.