| Sample / Model | Evidence (Microglia activation / Inflammasome / Downstream (cytokine) / Cell death / DA (& metabolites) / aSyn) |
|---|---|
| mouse primary microglia |
(Gordon, 2018 #586) [mouse primary microglia] MCC950 → i) ASC (이미) monomeric ASC induced by aSyn, fig3c,d), (Oligomeric ASC induced by aSyn, fig3ef), induced by ATP (FIG s6f), induced by nigericin (fig s6f) ii) ↓ cleaved caspase-1 (fig. S6A figs6d, fig3c,d), (Trudler, 2021 #1900) i) fig 2e, : siNLRP3 (KD)→ ↓ (oligomeric aSyn) -induced IL-1b i) fig s3, : MCC950 → ↓ (oligomeric aSyn) -induced IL-1b (Gordon, 2018 #586) [mouse primary microglia] IL-1b (induced by ATP, fig3a) (Induced by fibrillar aSyn, fig3b), induced by ATP (FIG s6e), induced by nig (fig s6e) (inhouse) TR06673219 → ↓ IL-1b |
| human iPSC-derived microglia (from normal fibroblast) | |
| (Control) hiPSC-derived microglia/neurons co-culture | |
| Casp1 inhibition (Wang, 2016 #2086) | (Wang, 2016 #2086) |
| Mice / aSyn pff |
(Gordon, 2018 #586) MCC950 → ↓ cleaved caspase-1 in the striatum of α-syn PFF-injected mice at 30 days (80% correction 30일간 투여)(Fig. 3H). (Gordon, 2018 #586) aSyn pff, MCC950 (po, 0.3 mg/ml, 8m) → fig6, ↓ (100% correction) NLRP3 (SN, WB), ↓ (90% correction) ASC (SN, WB), (Gordon, 2018 #586) (fig5) aSyn PFF model : counts of dopaminergic neurons in SN 6m 투여→ 반 correction (Gordon, 2018 #586) PFF:MCC950 → striatal dopamine concentrations (P < 0.01; Fig. 5H), |
| NLRP3 KO | |
| AAV-A53T-aSyn model, (prophylactic) (AAV1/2) → 1d 후 MCC950 (10w간) → kill / Uni Wurzburg |
the NLRP3 activation and TH loss were observed. MCC950 showed 50% reduction of NLRP3 activation after 20 mg/kg ip injection for 10 weeks MCC950 → (~100%) neuroprotection after 20 mg/kg ip injection for 10 weeks Inline figure (kept as evidence in `body_r02_c01.jpg`): bar chart `NEW! NLRP3 cells in SN` with annotations `3-fold` and `~50%` reduction; second bar chart panel `Validation of role of NLRP3 inhibition in neuroinflammation` (kept as evidence in `body_r02_c02.jpg`). |
| AAV-A53T-aSyn mouse | (Karikari 2022) IL-2 이 surgery 이후 5주께 증가이긴 하나, 기타 inflammation makrer 들 negative or 불명 |
| α-SYN PFF mouse | [Astellas] (symptomatic) model이네 α-SYN PFF dosed into the left striatum (for 13-14 wk → NLRP3 inh 4w) → Hanging wire test |
| ATG5 KO mice |
(Cheng, 2020 #1645) MCC950 (10mpk, 1m) → ↓ (60% correction) IBA1+ cells (SN)(fig5f) (Cheng, 2020 #1645) MCC950 (10mpk, 1m) → ↓ (60% correction) cleaved caspase-1, (fig5c) (Cheng, 2020 #1645) MCC950 → ↓ (100% correction) MIF (WB, fig5D), ↓ (100% correction) IL-1b mRNA, (Cheng, 2020 #1645) MCC950 → ↑ (90% correction) TH+Neurons (sn) (fig5j) |
| aSyn PFF / Nlrp3 inhibitor 아님. |
(Panicker, 2022 #2067) casp1 KO → ↑TH neurons (fig6h, ~half) (Panicker, 2022 #2067) casp1 KO → ↑TH (WB)(fig6k, ~half) |
| Bz-ATP | Inhouse, BzATP-treated mice : Inzomelid & TR06673219 → ↓ IL-1b |
| 6OHDA |
(Gordon, 2018 #586) MCC950 20 mpk → 6-OHDA model of PD (80% correction of p20 casp1, 투여기간 7day)(Fig. 3J). (Gordon, 2018 #586) 6OHDA Mice: DA neurons in SN (Fig. 4, H and I), MCC950 4w 투여→ 반 correction (Gordon, 2018 #586) MCC950 → ↓ striatal DA & DOPAC, HVA (이것들 다 100% correction, fig. 4, C to E) striatal (TH... |
| Mitopark | (Gordon, 2018 #586) MCC950 20 mpk → in MitoPark mice (투여기간 불상)(Fig. 3I) |
| Our plan; Atuka / (Intanigral) AAV-A53T-aSyn model, | TR0993, TR098, and TR660, (3-doses for) 2.5 months |
| NLRP3 KO+MPTP mice | (Ou, 2021 #1740) NLRP3 KO → protection of:::::: ↓ PD pathology (TH+ cells in SN (70% correction), DA ((90% correction), HVA ((60% correction), caspase-1 ((90% correction), NLRP3 (90% correction), IB-1b (90% correction), TNF-a, IL-... |
| NLRP3 KO+aSyn mice | 이게 부재! |
Cf) BzATP: 2’(3’)-O-(4-benzoylbenzoyl) adenosine 5’-triphosphate (, P2X7 agonist), {Bae, 2017 #1285} BzATP→ ↑ NLRP3 expression/activation, pro-IL-1β Active-form IL-1β (17kDa), caspase-1 p20
| 약 | Pathogen 청소 모델 | Downstream | 비고 |
|---|---|---|---|
| Pathogen이 없어져가는 모델, : bzATP (ivc에 최적은 아니구나) | 동료모집기능은 전천히 막는건지 모르겠으나, | Downatreatm 은 쌓인 것을 말끔히 치움. | |
| 중 | P1b: aSyn 불면 모델 P1b의 관건은 기왕것 청소 능력! 이에 최유사 동물모델은? | aSyn 계속 있어, NLRP3 level도 계속 있는 상태 | BzATP model 에서 ㅂ였듯이, 약이 NLRP3의 하류기능을 빨리 막고, (가정) 동료모집기능은 전천히 막는건가? |
| P2: TH사망은 비가역적이므로, i) 기왕청소를 한다면, Halting 까지가 가능할 것, reversal 은 불능, ii) 기왕청소 못 하면, slowing 이 목표. | |||
| 심 | 예방 모델: Wurzbur | aSyn 증가중 | |
| 예방모델: ATG5 (conditional) KO | 불량 lysosome 출현했지만, | 약이 nlrp3의 동료모집 기능을 막음 (반). → nlrp3 level 이 반만 증가 | |
| 예방vs치료 불명 | Pathogen이 매우 천천히 없어져가는 모델, : 6ohda | 동료모집기능은 전천히 막는건지 모르겠으나, | Downatreatm 은 쌓인 것을 7일만에 (거의) 말끔히 치움. (Gordon, 2018 #586) fig 3J |
Uncertain Spans
| location | transcription | uncertainty |
|---|---|---|
central matrix / column placement | the central matrix has six target columns (Microglia activation / Inflammasome / Downstream (cytokine) / Cell death / DA (& metabolites) / aSyn) per the status-bar body strip; in the main body the cell boundaries are partly cut off and the per-target citation column placement is collapsed into one logical Evidence cell per model row. | column placement marked uncertain; original separation should be re-derived by reading the same table on adjacent photos. |
Mice / aSyn pff cell | reads (Gordon, 2018 #586) MCC950 → ↓ cleaved caspase-1 in the striatum of α-syn PFF-injected mice at 30 days (80% correction 30일간 투여)(Fig. 3H). and the next paragraph reads (po, 0.3 mg/ml, 8m); the 8m token is highlighted yellow. | low confidence on whether 8m denotes 8 months or 8 weeks. |
Astellas row | reads [Astellas] (symptomatic) model이네 α-SYN PFF dosed into the left striatum (for 13-14 wk → NLRP3 inh 4w) → Hanging wire test; the 13-14 wk token is partly clipped. | low confidence on 13-14 wk interval. |
bottom Korean table / 약 column entries | the leftmost 약 column entries 중, 심 are visible single Korean characters that may denote drug-state labels (medium / severe?); preserved verbatim. | low confidence on intended meaning. |