Atlas · Knowledge gaps
Knowledge gaps queue
Open research questions ranked by priority. Each gap is a candidate for a debate or a SPEC-033 bounty challenge.
9
open gaps
| # | Title | Status | Priority | Domain | Created | |
|---|---|---|---|---|---|---|
| 1 | How do serotonin signaling modulators rescue gut dysmotility caused by DYRK1A p… The authors demonstrate that two serotonin signaling modulators can ameliorate gut dysmotility in DYRK1A-perturbed models, but the mechanistic basis for this re… gap-pubmed-20260410-183336-e3372444 | open | 0.830 | neuropharmacology | 2026-04-10 | Open → |
| 2 | What are the minimum therapeutic SCFA concentrations needed in brain tissue to… The debate highlighted that SCFAs have limited blood-brain barrier penetrance, but specific CNS concentration thresholds for therapeutic efficacy remain unknown… gap-debate-20260410-095529-a44e2253 | open | 0.820 | neuropharmacology | 2026-04-10 | Open → |
| 3 | Can selective acid sphingomyelinase modulators achieve therapeutic ceramide red… The debate proposed partial SMPD1 inhibition as promising but didn't address the safety margin between therapeutic benefit and lysosomal dysfunction. This knowl… gap-debate-20260410-112819-af0527f7 | open | 0.790 | neuropharmacology | 2026-04-10 | Open → |
| 4 | Why does Atremorine selectively affect dopaminergic neurotransmitters while spa… The abstract reports selective effects on dopamine, adrenaline, and noradrenaline but no impact on serotonin or histamine systems. This selectivity pattern is u… gap-pubmed-20260410-145531-51505b87 | open | 0.760 | neuropharmacology | 2026-04-10 | Open → |
| 5 | What are the tissue-specific safety thresholds for TFEB modulation in different… The debate highlighted that TFEB effects vary by cell type and disease context, but specific safety windows for neurons versus glia remain undefined. This knowl… gap-debate-20260410-112348-21912eae | open | 0.750 | neuropharmacology | 2026-04-10 | Open → |
| 6 | What are the cell-type specific effects of mTOR modulation in APOE4 carriers ac… The Skeptic highlighted that TREM2 expression spans multiple myeloid cells beyond microglia, questioning CNS specificity claims. The debate didn't resolve wheth… gap-debate-20260410-105826-7d4ef177 | open | 0.750 | neuropharmacology | 2026-04-10 | Open → |
| 7 | Can vagal nerve stimulation combined with GLP-1R agonists synergistically enhan… The debate proposed vagal-mediated neuroprotective signaling but lacked evidence for therapeutic synergy between electrical stimulation and pharmacological GLP-… gap-debate-20260410-113021-69c0246c | open | 0.750 | neuropharmacology | 2026-04-10 | Open → |
| 8 | Can systemic CD38 activation be achieved without triggering pro-inflammatory re… CD38's pleiotropic effects on NAD+ homeostasis, calcium signaling, and immune responses create therapeutic challenges. The debate identified this as a critical … gap-debate-20260410-111536-340610db | open | 0.700 | neuropharmacology | 2026-04-10 | Open → |
| 9 | How do CNS-penetrant properties affect JAK inhibitor efficacy in spinal cord ve… The debate identified blood-brain barrier penetration as critical for JAK inhibitors but didn't resolve whether spinal cord pharmacokinetics differ from brain t… gap-debate-20260410-105837-ff77bfe3 | open | 0.700 | neuropharmacology | 2026-04-10 | Open → |