mechanism 3,010 words KG: ent-gene-677b2317 2026-03-23
kind:mechanismsection:mechanismsstate:publishedevidence:strong
Contents

Sigma-1 Receptor Signaling in Neurodegeneration

🔬 Protein Info
Gene Symbolent-gene-677b2317
Subcellular Localizationthe endoplasmic reticulum (ER) membrane, particularly at the ER-mitochondria interface (MAMs - mitochondrial-associated
PRE-084A highly selective sigma-1 receptor agonist that has demonstrated neuroprotective effects in multiple models of neurodegeneration [@pre]
SA-4503 (Cutamesine)Showed promise in clinical trials for stroke recovery and has been investigated for neurodegenerative diseases [@cutamesine]
DextromethorphanA commonly used antitussive that also possesses sigma-1 agonist activity
DonepezilAn approved acetylcholinesterase inhibitor for Alzheimer's disease that also acts as a sigma-1 agonist [@donepezil]
FluvoxamineAn SSRI antidepressant with sigma-1 agonist properties [@fluvoxamine]
HaloperidolA typical antipsychotic with sigma-1 antagonist activity
BD1063A selective sigma-1 antagonist used in research
NE-100A potent and selective sigma-1 antagonist
ER Calcium HomeostasisSigma-1 regulates calcium release through IP3Rs and ryanodine receptors, preventing pathological calcium depletion from ER stores
Mitochondrial Calcium UptakeBy modulating VDACs and the mitochondrial calcium uniporter (MCU), sigma-1 controls mitochondrial calcium levels essential for ATP production
Calcium BufferingIn neurons, proper mitochondrial calcium buffering is crucial for synaptic function and survival
Store-Operated Calcium EntrySigma-1 modulates STIM1 and Orai1 function, affecting store-operated calcium entry mechanisms
KG Connections2 knowledge graph edges
DatabasesGeneCardsUniProtNCBI GeneHPASTRING

Knowledge Graph

Related Hypotheses (30)

Nutrient-Sensing Epigenetic Circuit Reactivation
Score: 0.88
SASP-Mediated Complement Cascade Amplification
Score: 0.87
Selective Acid Sphingomyelinase Modulation Therapy
Score: 0.86
CYP46A1 Overexpression Gene Therapy
Score: 0.86
Transcriptional Autophagy-Lysosome Coupling
Score: 0.84

Related Analyses (30)

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Related Experiments (30)

ER-Golgi Secretory Pathway Dysfunction in PD - Experiment De
clinical · proposed · Score: 0.40
Macroautophagy Dysfunction in PD - Experiment Design
clinical · proposed · Score: 0.40
Proposed experiment from debate on Astrocytes adopt A1 (neur
falsification · proposed · Score: 0.40
s:** - Biochemical binding assays measuring PROTAC selectivi
falsification · proposed · Score: 0.40
Proposed experiment from debate on Epigenetic clocks and bio
falsification · proposed · Score: 0.40

See Also (15)

Yoga Therapy for Neurodegeneration
therapeutic · Pages share 139 hypotheses
YAP/TEAD Pathway Modulators for Neurodegeneration
therapeutic · Pages share 139 hypotheses
Wnt Signaling Modulators for Neurodegeneration
therapeutic · Pages share 139 hypotheses
vitamin-d-therapy-neurodegeneration
therapeutic · Pages share 139 hypotheses
Vitamin B Complex Therapy for Neurodegeneration
therapeutic · Pages share 139 hypotheses

Knowledge Graph (2 edges)

ent-gene-677b2317 data_in benchmark_ot_ad_answer_key:SIGMA1
benchmark_ot_ad_answer_key:SIGMA1 data_in ent-gene-677b2317

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