| a lack of induction of A20 (A20 is a microglia-enriched protein and a well-known negative regulator of the NF-κB pathway) (Mouton-Liger, 2018 #1216) | ↑ Microglial NLRP3 inflammasome activation (Mouton-Liger, 2018 #1216, KO Mice-derived microglial culture) | (Mouton-Liger, 2018 #1216) ↑ IL-1b and IL-18 in Park2-/- and Pink1-/- cells. This defect was confirmed in blood-derived macrophages from patients with PARK2 mutations and was reversed by MCC950 | |||||||
| aSyn PFF mouse | =parkin protein, but ↓ parkin autoubiquitination (wb, 2022 panicker #20670 | - ↑ NLRP3 (2022 Panicker #2067) fib6b (wb) | - ↑ casp1 p20 (2022 #2067) fib6b (wb) | ↑ DA neuron death (2022 #2067) fib6 (wb) | |||||
Pyroptosis evidence/MOA/Correction in PD
| Microglia activation | Inflammasome | Downstream (cytokine) | Cell death | DA (& metabolites) | aSyn | ||||
|---|---|---|---|---|---|---|---|---|---|
| Human | Gene | ||||||||
| Brain (Postmortem) | ↑ CD4+ T lymphocytes infiltration (SN & amygdala), increased inflammatory markers such as (HLA-DR), (MHCII), phagocytic marker CD68, intercellular adhesion molecule-1 (ICAM-1), and integrin adhesion molecule (LFA-1) in SN [6, 7]. | (Gordon, 2018 #585) fig 1) IBA1+ cells (SN): staining figure but no quantification | (Gordon, 2018 #585, n=6 each, PD stage not specified) fig 1) ↑ NLRP3 & ASC (IF) in IBA-1-positive microglia in patient (정량화x), 아래그림은 (fig1b) WB. |
- (Mogi, 1994 #654) PD (n=9), PD stage not specified, : In striatum & Frontal cortex in PDD/PDND) above table mean w SEM ↑ IL-1β, ↑ TLR4 내가 sd로 바꿔 d 계산하니 1.03 for IL-1b | Not mention | (Wang, 2016 #639) Costaining of αSyn and caspase-1 in the autopsy brain of PD patients. | |||
| Postmortem: |
(Smajić, 2020 #1812) ↑ microglia (fig2c cd74, fig2e IBA1) (Kouli, 2020 #1209) ↑ Activated microglia (HLA-DR+) in PDD amygdala |
(Panicker, 2022 #2067) SNpc lysates, (n=6), NLRP3 & Casp1-20 (WB, fig7a) & IHC in SNpc (fib7b: NLRP3 in DA neurons), (fig7c: ↑ casp1 & ASC speck in DA neurons) Severity와 correlation 되는 셋중하나 증거 (Anderson, 2021 #1266, histology, suppl fig1에서 IBA1과 NLRP3의 colocalisation 봤으나 정량화x, selectivity 평가x) n=6 each group, 아래그림은 그냥 (cell type고려x) NLRP3/ASC positive cell의 개수임. 근데, 아래 n은 군간 mean이 다름을 보이는데 필요한 수이지, differentiation 용이 아님! | Not mention | ↑ a-syn in the hippocampus, entorhinal and occipitotemporal cortex of PDD (vs PDND) | |||||
| Postmortem | (von Herrmann, 2018 #1795) (mesencepahlon) 17 PD, 11 HC, (fig1b) ↑ The average percentage of neuromelanin-pigmented positive neurons (50 neurons counted per section) (NLRP3-positive cells were ~60% in PD, ~20% in HC), (fig1d) ↑ mean NLRP3 IF intensity (fig1e) ↑ NLRP3 mRNA (bulk), Suppl fig1b) ↑ zymogen casp1, Suppl fig1c) ↑ p10 subunit of casp1 (정량화x), p45 (WB, supple fig1b) huge ↑ | Not mention | Average pigmented cell bodies count (fig1a, histology, Estimations of DA neuron density). | ||||||
| CSF | • | 2009 Hirsch에 엄청많음 | • | (Zhang, 2016 #583) n=8 PD patients, ↑ IL-1β & ↑ IL-18 | |||||
| CSF | • |
(Chen, 2018 #1635} metaanalysis (4개 source paper 뒤져 합치니 n=123 PD) Hedges g (95% CI): 0.37 (0.033 to 0.707) | |||||||
| CSF | • | (Hu, 2015 #1794) ↑ IL-1β [median (quartile)] (pg/ml) Control (N=31): 9.409 (8.535~36.169), nprbd (N=51, 대개 early): 11.122 (8.862~69.511), pbrd (대개 early, N=16): 67.032 (10.438~146.820) | |||||||
| CSF | • |
(Pirttila, 1994 #1796) = IL1b (n=20) (Mogi, 1996 #1797) ↑ IL-1β in PD (n=14), 좀 겹침 | |||||||
| Blood | • |
- (Blum-Degena, 1995 #653) PD (n=22), ↑ IL-1β in CSF & plasma (Qin, 2016 #1860) MA n=623 PD vs 339 HC, hedges g 0.382) | |||||||
| Serum | • |
(Roy, 2022 #2080) [longitudinal] (early to mod) PD20, HC16, cross-sectinally: NLRP3 (not il-1b) significantly correlated with H&Y (Fig3), but longitudunally, Over 1y, NLRP3 & il-1b increased in parallel. But We didn't observe any correlation between extent of changes in disease severity and peripheral BM in the PD cohort (P>0.05). (Williams-Gray, 2016 #1862) ? | |||||||
| serum | • |
Uncertain Spans
| location | transcription | uncertainty |
|---|---|---|
| aSyn PFF mouse row | 2022 panicker #20670 | trailing digit may be 2067 rather than 20670; closing parenthesis is adjacent to the digit. |
| Smajić citation | Smajić, 2020 #1812 | diacritic on Smajić not crisp at this zoom. |
| Williams-Gray cell | (Williams-Gray, 2016 #1862) ? | only citation header is fully visible; remainder clipped at edge of photo. |