s:**
- GPR32 knockout in microglia should worsen neuroinflammation if this is the primary mechanism
- Dose-response stud
🧬 GPR32
🏥 Neuroinflammation
🔗 5 hyp
💰 $80,000
⏱ 5mo
✅ 0.50
✨ 0.50
**Phase 1: Cell Line Preparation and Genetic Modification (Days 1-14)**
Expected: **GPR32 knockout microglia will show 2-3 fold increased pro-inflammatory cytokine production** (TNF-...
s:**
- ALOX15 overexpression in healthy astrocytes should be protective if the hypothesis is correct
- Measure both pro-
🧬 ALOX15
🏥 Neuroinflammation
🔗 5 hyp
💰 $200,000
⏱ 8mo
✅ 0.50
✨ 0.50
**Phase 1: Mouse Model Preparation (Weeks 1-2)**
Expected: **Enhanced LXA4 Production**: ALOX15 overexpression should increase LXA4 levels by 3-5 fold compared...
Proposed experiment from debate on Astrocytes adopt A1 (neurotoxic) and A2 (neuroprotective) phenotypes, but recent
🧬 BMAL1
🏥 Neurodegeneration
🔗 5 hyp
💰 $80,000
⏱ 5mo
✅ 0.50
✨ 0.50
**Phase 1: Cell Culture Preparation (Days 1-2)**
Expected: **Circadian oscillation of A1/A2 markers**: WT astrocytes will show 24-hour rhythmic expression of p...
Proposed experiment from debate on TDP-43 undergoes liquid-liquid phase separation that becomes pathological. Small
🧬 TDP
🏥 Neurodegeneration
🔗 5 hyp
💰 $80,000
⏱ 5mo
✅ 0.50
✨ 0.50
**Phase 1: Cell Culture Preparation (Days 1-3)**
Expected: Peptide mimetics will demonstrate 3-5 fold selectivity for disrupting pathological TDP-43 aggregates...
Proposed experiment from debate on TDP-43 undergoes liquid-liquid phase separation that becomes pathological. Small
🧬 G3BP
🏥 Neurodegeneration
🔗 5 hyp
💰 $80,000
⏱ 5mo
✅ 0.50
✨ 0.50
**Phase 1: Cell Culture Preparation (Days 1-3)**
Expected: **TDP-43 aggregation will persist in G3BP-inhibited cells**, with ≥70% of transfected cells showing ...
Proposed experiment from debate on Microglia activate astrocytes via IL-1alpha/TNF/C1q, and reactive astrocytes fee
🧬 DREADD
🏥 Neurodegeneration
🔗 5 hyp
💰 $100,000
⏱ 5mo
✅ 0.50
✨ 0.50
**Phase 1: DREADD Construct Preparation and Validation (Weeks 1-2)**
Expected: **DREADD expression stability**: >80% of transduced cells maintain detectable DREADD expression at 2...
s:**
- Compare tau strain spreading in EXT1/EXT2 conditional knockout mice
- Test whether HSPG-deficient astrocytes stil
🧬 EXT1
🏥 Neurodegeneration
🔗 5 hyp
💰 $260,000
⏱ 9mo
✅ 0.50
✨ 0.50
**Phase 1: Animal Preparation and Genotyping (Weeks 1-2)**
Expected: **Reduced tau pathology spreading**: EXT1/EXT2 cKO mice will show 40-60% reduction in tau-positive n...
s:**
- Test tau spreading in AQP4 knockout vs wild-type mice with PSP/CBD strains
- Rescue AQP4 polarization pharmacolog
🧬 AQP4
🏥 Neurodegeneration
🔗 5 hyp
💰 $260,000
⏱ 9mo
✅ 0.50
✨ 0.50
**Phase 1: Animal Preparation and Genotyping (Weeks 1-2)**
Expected: **Increased tau pathology spread in AQP4 knockout mice**: AQP4-/- mice will show 40-60% greater tau ...
Proposed experiment from debate on Perivascular spaces and glymphatic clearance failure in AD
🧬 TREK
🏥 Neurodegeneration
🔗 5 hyp
💰 $240,000
⏱ 9mo
✅ 0.50
✨ 0.50
**Phase 1: Animal Preparation and Baseline Characterization (Days 1-7)**
Expected: **AQP4 polarization enhancement**: TREK-1 activation with ML335 will increase AQP4 polarization inde...
Proposed experiment from debate on Perivascular spaces and glymphatic clearance failure in AD
🧬 PDGFR
🏥 Neurodegeneration
🔗 5 hyp
💰 $100,000
⏱ 5mo
✅ 0.50
✨ 0.50
**Phase 1: Cell Culture Preparation (Days 1-7)**
Expected: **Selective pathway activation**: PI3K-biased agonist will increase p-AKT levels 3-5 fold while main...
s:**
- Test whether HCN1 knockout specifically in EC layer II accelerates or protects against AD pathology
- Measure whe
🧬 HCN1
🏥 Alzheimer's Disease
🔗 5 hyp
💰 $80,000
⏱ 5mo
✅ 0.50
✨ 0.50
**Phase 1: Cell Culture Preparation (Days 1-7)**
Expected: **HCN1 knockout in EC layer II neurons will accelerate AD pathology**, showing 30-50% increased tau ...
s:**
- Test MCU overexpression specifically in layer II neurons in healthy vs
🧬 MCU
🏥 Neurodegeneration
🔗 5 hyp
💰 $200,000
⏱ 8mo
✅ 0.50
✨ 0.50
**Phase 1: Animal Preparation and Genotyping (Weeks 1-2)**
Expected: **MCU overexpression increases mitochondrial calcium uptake by 40-60%** in both healthy and AD model...
Proposed experiment from debate on Senolytics targeting p16/p21+ senescent astrocytes and microglia may reduce SASP
🧬 BCL2L1/C1Q/C3
🏥 Neurodegeneration
🔗 5 hyp
💰 $80,000
⏱ 5mo
✅ 0.50
✨ 0.50
**Phase 1: Cell Culture Preparation (Days 1-7)**
Expected: **Direct lipid peroxidation transfer**: Fluorescent lipid peroxidation products will transfer from s...
s:**
- Dose-response studies showing therapeutic window without toxicity
- Cell-type specific effects across CNS populat
🧬 DNAJB1/DNMT1/FKBP5
🏥 Neurodegeneration
🔗 5 hyp
💰 $80,000
⏱ 5mo
✅ 0.50
✨ 0.50
**Phase 1: Cell Line Preparation and Characterization (Days 1-3)**
Expected: **Dose-dependent toxicity curve**: IC50 values >100 μM for enhanced formulation vs. <50 μM for stand...
s:**
- Temporal analysis showing mitochondrial defects precede other pathology
- Rescue experiments in isolated mitochon
🧬 RBP
🏥 Neurodegeneration
🔗 5 hyp
💰 $80,000
⏱ 5mo
✅ 0.50
✨ 0.50
**Phase 1: Cell Line Preparation and Characterization (Days 1-7)**
Expected: **Mitochondrial dysfunction precedes other pathology**: ATP levels decrease by ≥30% within 24-48h of...
s:**
- Compare brain penetration in FcRn+/+ vs FcRn-/- mice with engineered vs native antibodies
- Test whether pH-modif
🧬 ABCB1/C1QA/CAV1
🏥 Neuroinflammation
🔗 5 hyp
💰 $200,000
⏱ 8mo
✅ 0.50
✨ 0.50
**Phase 1: Animal Preparation and Genotyping (Days 1-7)**
Expected: **Reduced brain penetration in FcRn-/- mice**: Native antibodies show 60-80% decreased brain accumul...
s:**
- Compare uptake with/without magnetic particles using tight junction integrity markers
- Test whether clustering o
🧬 ABCB1/CAV1/CLDN5
🏥 Neurodegeneration
🔗 5 hyp
💰 $120,000
⏱ 5mo
✅ 0.50
✨ 0.50
**Phase 1: Cell Culture Preparation (Days 1-7)**
Expected: **Tight junction integrity compromise**: Magnetic particles will reduce TEER by 25-40% compared to n...
Proposed experiment from debate on Epigenetic clocks and biological aging in neurodegeneration
🧬 HDAC3
🏥 Neurodegeneration
🔗 5 hyp
💰 $100,000
⏱ 5mo
✅ 0.50
✨ 0.50
**Phase 1: Cell Line Establishment and Baseline Characterization (Weeks 1-4)**
Expected: **Epigenetic Age Deceleration**: HDAC3 inhibition will reduce epigenetic age acceleration by 15-30% ...
Proposed experiment from debate on Synaptic pruning by microglia in early AD
🧬 C1Q/C1QA/C3
🏥 Alzheimer's Disease
🔗 5 hyp
💰 $200,000
⏱ 8mo
✅ 0.50
✨ 0.50
**Phase 1: Animal Preparation and Randomization (Weeks 1-2)**
Expected: C1q decoy treatment will reduce synaptic pruning by 40-60% compared to vehicle controls in APP/PS1 m...
Proposed experiment from debate on Synaptic pruning by microglia in early AD
🧬 CX3CR1
🏥 Neuroinflammation
🔗 5 hyp
💰 $240,000
⏱ 9mo
✅ 0.50
✨ 0.50
**Phase 1: Experimental Setup and Model Validation (Weeks 1-2)**
Expected: **Dose-dependent anti-inflammatory response**: Medium and high dose PAM treatments will reduce pro-i...
Proposed experiment from debate on Mitochondrial transfer between astrocytes and neurons
🧬 TNT
🏥 Neurodegeneration
🔗 5 hyp
💰 $100,000
⏱ 5mo
✅ 0.50
✨ 0.50
**Phase 1: Cell Culture Preparation (Days 1-3)**
Expected: **TNT Stability Enhancement**: GAP43-overexpressing astrocytes will show 2-3 fold increase in TNT li...
Proposed experiment from debate on Mitochondrial transfer between astrocytes and neurons
🧬 TFAM
🏥 Neurodegeneration
🔗 5 hyp
💰 $80,000
⏱ 5mo
✅ 0.50
✨ 0.50
**Phase 1: Cell Culture Preparation (Days 1-7)**
Expected: **TFAM overexpression increases mitochondrial transfer rates by 2-3 fold** compared to control astro...
s:**
- Single-cell RNA-seq to measure editing efficiency across different CNS cell types
- Genome-wide off-target analys
🧬 HNRNPA2B1/SETX/TARDBP
🏥 ALS
🔗 5 hyp
💰 $150,000
⏱ 6mo
✅ 0.50
✨ 0.50
**Phase 1: Cell Line Preparation and Editing (Weeks 1-2)**
Expected: On-target editing efficiency of 60-85% in motor neurons and 45-70% in astrocytes, with motor neurons...
s:**
- Biochemical binding assays measuring PROTAC selectivity for APOE4 vs APOE3
- Mass spectrometry-based degradation
🧬 PROTAC
🏥 Neurodegeneration
🔗 5 hyp
💰 $100,000
⏱ 5mo
✅ 0.50
✨ 0.50
**Phase 1: PROTAC Synthesis and Characterization (Weeks 1-2)**
Expected: **APOE4 selectivity**: PROTAC demonstrates >10-fold binding selectivity for APOE4 vs APOE3 (KD-APOE4...
Proposed experiment from debate on Epigenetic clocks and biological aging in neurodegeneration
🧬 TET2
🏥 Neurodegeneration
🔗 5 hyp
💰 $450,000
⏱ 13mo
✅ 0.50
✨ 0.50
**Phase 1: Animal Preparation and Baseline Assessment (Weeks 1-4)**
Expected: **Cognitive Performance**: TET2 overexpression mice will show 15-25% improvement in spatial memory t...
Proposed experiment from debate on Astrocytes adopt A1 (neurotoxic) and A2 (neuroprotective) phenotypes, but recent
🧬 HK2
🏥 Neurodegeneration
🔗 5 hyp
💰 $100,000
⏱ 5mo
✅ 0.50
✨ 0.50
**Phase 1: Cell Culture Preparation (Days 1-3)**
Expected: **HK2 inhibitor treatment will promote A1 phenotype adoption**: 2-3 fold increase in A1 markers (C3,...
Proposed experiment from debate on Microglia activate astrocytes via IL-1alpha/TNF/C1q, and reactive astrocytes fee
🧬 PLIN2
🏥 Neuroinflammation
🔗 5 hyp
💰 $80,000
⏱ 5mo
✅ 0.50
✨ 0.50
**Phase 1: Cell Culture Preparation (Days 1-3)**
Expected: **Enhanced lipid droplet formation**: PLIN2-overexpressing astrocytes will show 2-3 fold increase in...