Spotlighting Sigma-1 Receptor: A Novel Approach for Phenotypic Modulation Over Classical Target Inhibition
- The role of sigma-1 receptor as a broad anti-inflammatory mediator, impacting multiple cytokines beyond single targets like TNF-alpha
- Use of phenotypic screening approaches focusing on reversing disease-related impairments (e.g., cognitive deficits caused by amyloid-beta 1-42 in Alzheimer’s) rather than directly blocking pathogenic molecules
- Evidence that targeting impairments downstream of toxic proteins, rather than the proteins themselves, may offer more effective and practical therapeutic strategies
- Comparison with other inflammatory targets such as NF-kappa B, highlighting sigma-1 receptor’s broader and potentially safer anti-inflammatory profile
- The paradigm shift from target-centric to phenotype-driven drug discovery, where finding drugs that work precedes elucidating their precise mechanisms