총정리 GBA protein & activity (continued)
Cathepsin D activity HC vs GBA+PD: not significant
PBMC
| Citation | Sample | Notes | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| (Huh, 2020 #1105) | Dried blood spot (Perkin Elmer) |
GBA activity no reduction overlap! GBA activity 대략 60% of healthy control GlcCer, GlcSph는 논문x | ||||||||||||||
| (Lorincz, 1997 #796) | PBMC (culture 아닌듯, CBE 줄때는 culture에) |
Type 1 GD patients (n=6) GBA activity: 10% (PBMC), monocyte도 유사결과 | ||||||||||||||
| (Narita, 2016 #560) | Lymphocyte |
[nGD] 10-30% of control (표3), recovered by ambrosol | ||||||||||||||
| (Blumenreich, 2022 #2619) | Postmortem brain |
N=21, GlcCer: =, GlcSph: not done | ||||||||||||||
| (Li, 2019 #2553) | Postmortem brain |
(fig7) ↓ GBA protein (60%) & activity (40%) Mito: ↑ VDAC, ↓ MC1 enz activity, ↑ 8-OHdG, CYCS ↑, ↓ TOMM20, ↓ TIM23, ↓ MFN1 &2, OPA1, ↓ DNM1L, ↓ FIS1 Lyso: fig8, ↑ lc3ii, ↑ lc3b, ↑ sqstm, ↑ (trend) LAMP1, ↑ SQSTM1, ↓(p-MTOR, p-RPS6, AMBRA1, BECN1) Cf) GbaL444P/WT mouse hippocampal neurons data available | ||||||||||||||
| (Ambrosi, 2015 #747) | Fibroblast |
↓ GBA activity (js 50%, this is corrected by ambroxol, fig1), slightly ↓ GBA protein (js 10%), =Prosaposin, =saposin,) Cathepsin activity (increased by ambroxol, fig2) =LIMP2 (fig3) increased by am-broxol | ||||||||||||||
| (McNeill, 2014 #236) | Fibroblast |
↓ GBA activity (fig1), ↑ (β-hexosaminidase, essential for the degradation of GM2 gangliosides), ↑(오히려) cathepsin D wb를 정량화는 안 함) Fig4, (LC3II, p62 이 둘은 =), = LAMP1 (fig4) All type1 GD,) ↑ GlcSph (fig1) Cf) ↑ GlcSph in control fibroblasts by CB (이 부분 안 뵈는데?) ↑ (β-hexosaminidase.), and cathepsin D, Fig4, (LC3II, p62 이들은 =) | ||||||||||||||
| (Fernandes, 2016 #741) | iPSC-derived dopaminergic neurons (N370S heteroz) |
(fig6) ↑ cathepsin D (wb) ↑ LAMP1, ↑ LAMP2a, ↑ LIMP2 (이것만 fig2d), ↓ GBA Activity(50%), ↑ p62 ↑ lysosomal number with undegraded cargo(fig 5), ↑ beclin1 | ||||||||||||||
| Papagannakis, 2015 #753) 2nd | PBMC |
reduced Lamp2a mRNA and protein levels in PBMCs, whereas Sala and colleagues26 showed decreased Hsc70 protein and mRNA levels in PD PBMCs without changes in Lamp2a levels. | ||||||||||||||
| Ivanova, 2019 #759) 중요. | PBMC, 근데 논문에서 GD1과 GD3의 결과를 구분하자! |
[basal] ↓ GBA protein (type1 GD, WB, SFig4), GBA activity는 안 봤. ↓ autophagosome, ↑ lysosomal accumulation, ↑ beclin1 ↑ LAMP1, ↓ LC3II, ↓ p62. [ERT후] autophagosome level fig4에선= fig5에선 복원,, LAMP1정상화, ↓ LC3I, [Ambroxol후] fig4D, ↑ conversion of LC3I→LC3II | ||||||||||||||
| Papagannakis, 2015 #753 | PBMC, mitochondria |
↓ (js 50%, fig2c) ↑ (2x) (저자; compensation) ↓ (js 40%), overlap 되는듯 (fig2D) ↓ (js 50%), overlap될듯말듯 = (compensation인가?) | ||||||||||||||
| ollins, 2017 #715 | Skin fibroblast |
GBA protein: N=3 GBA activity: N=3, absent, N=4, N=3 Differentiated from normal control | ||||||||||||||
|
LC3IIb Gold nanoparticle (AuNPS) assay α-galactosidase activity, Hexosaminidase activity, Mannosidase activity |
Altered (fib2), ie treaetment response to Bafilomycin A1 is altered. No difference Altered? | |||||||||||||||
| chez-tinez, 2016 | Skin fibroblast |
GBA protein: Non significantly reduced (30%?) GBA activity: ↓ (js 50%), ↓ (js 30%) 약간 overlap, | ||||||||||||||
| elina, 2014 #3 | Plasma |
= (fig2) ↑ aSyn oligomer (4x, overlap) (fig2) | ||||||||||||||
| ga, 2016 | Blood, GBA activity only |
↓ ↓↓ | ||||||||||||||
| hrazm et al. PMID) | monocytes – GBA activity (by flow cytometry) |
N=39) GCase activity was significantly reduced in monocytes, but not lymphocytes, compared to controls Monocyte GCase activity correlated with plasma ceramide levels in the Parkinson's disease patients. GBA activity: N=9) PD only보다 조금 더 감소된 듯. FIG4의 a,b조합하면, normal:30, GBA-PD:22, GBA+PD:20정도로 보임 다음은 논문에 없으니 이상? ↑ oligomeric aSyn (n = 41, GD TYPE 불명), (RBCs) are the main source of aSyn in blood, and plasma protein levels could be artificially elevated by contamination of intact or lysed RBCs due to their abundance and fragility | ||||||||||||||
| et al. PMID 366) (DBS) cohort |
DBS cohort – GBA protein GBA activity (by mass spectrometer ie MS/MS, using an artificial substrate) GBA mRNA |
N=48 (Spd + gbaPD), GBA activity was not correlated with age, disease duration, H&Y scale, age at diagnosis, levodopa equivalent dose, time to blood draw. Not done Very slightly ↓ (-5%, 11.53 vs 12.11 in control), (Table4, baseline) Lower GBA activity tertile (ie 8.59 umol/l/h): ↓ UPDRS-III, higher MOCA, ↓ disease duration, older AAO, shorter disease duration), js, no conclusion from this! (n=81) 66.5% (mean 7.88, sd not said) of control, Overlap?) control 11.85 (3.40), so significant overlap (fig1b, 75% percentile in gba+pd seems 9.5, so almost 64% overlap!) Seems NA PD+GBA Homoz 7.2% of control (0.85) |
Uncertain Spans
| location | transcription | uncertainty |
|---|---|---|
| whole page column structure | the original wide matrix has PD only / PD+ heteroz / Hetero only / GD only / PD+GD result columns plus additional GlcCer / GlcSph commentary columns | The transcription preserves each row’s visible body text in a single Notes cell because exact column placement of every result phrase is not consistently legible from a single capture; refer to the body_full evidence and adjacent photo 20240722_182123 for cross-row column placement. |
| Ambrosi row | =saposin,) | the cell ends with an unmatched ); preserved as visible source. |
| Papagannakis 2015 PBMC mitochondria | the inner sub-table value list | The values ↓ (js 50%, fig2c) etc. are listed below the column-name table; their exact mapping to GBA Protein / mRNA / activity / HSC70 etc. is not unambiguous from the visible crop and is preserved as a list. |
| Citation column / clipped rows | ollins, 2017 #715, chez-tinez, 2016, elina, 2014 #3, ga, 2016, hrazm et al. PMID), et al. PMID 366) | The leftmost citation cells are clipped at the photo edge; only the visible portions of the names/PMIDs are preserved. |
| DBS cohort row | 8.59 umol/l/h, UPDRS-III, MOCA, AAO, 66.5% (mean 7.88, sd not said), 11.85 (3.40), 9.5, 64% overlap, 7.2% of control (0.85) | The dense numeric notes span multiple narrow cells; values should be cross-checked with the body_full evidence before downstream use. |
| Cathepsin D activity continuation header | Cathepsin D activity / HC vs GBA+PD: not significant / PBMC | The three lines are visible at the very top of this capture and continue from 20240722_182123’s figure description. |
| Li / Mito / Lyso row | symbol direction (↑/↓/=/(trend)) | The dense up/down arrows are small in the visible crop and should be verified against the body_full evidence before quantitative interpretation. |