총정리 GBA protein & activity POSTMORTEM (continued)
L444P and R463C point mutation mouse(Ginns,) in Striatum (hetero는 안 쓰인 것 같음) CBE (Manning-Bog, midbrain) CBE (Ginns) in SN & Straitum CBE 100mg, 28 d (Rocha) → ↑ proteinase-K resistant a-syn aggregates
(Papadopoulos, 2018 #1273) CBE+A53T mice: ↑ aSyn soluble monomer in midbrain, striatum aSyn oligomer, (but no change in p-aSyn,), see additional details of Asyn different species and different regions.
(Henderson, 2020 #1233) In PFF-treated mice: CBE → ① = dopaminergic neuronal loss in SN (fig 5F), ② GCase inhibition does not induce aggregation of a-syn but rather induces mild neuronal spheroids recognized by 81A, which can cross-react with neurofilament ③ 거의, = aSyn spread (to cortex) fig 6B
Synapse
In Vitro
In VIVO (Rocha, 2015 #1253) CBE (100mg/kg, 28 d) → c1q, SNAP-25, Synaptophysin, synaptoagmin, synapsin, PSD-95
총정리 GBA protein & activity POSTMORTEM] Activity: hetero only 에선 kurzawa가 유일.
- GlcSph
- Blood: 에서 단독으로 본 것 없잖아!? (2017 Guedes에선 galactosylsph와의 sum), 이거 못 보나 Sato에게 물어보자.
| sample | GBA protein | GBA activity | GlcCer | GlcSph | Cathepsin D protein | Cathepsin D activity | LIMP2 | LAMP2 | LC3 |
|---|---|---|---|---|---|---|---|---|---|
| GBA+PD / Brain |
(Li, 2019 #745) In supplement (Gundner et al. 2019, PMID 30236861) (Gegg et al. 2012, PMID 23034917) (Choi et al. 2011, PMID). (Kurzawa-Akanbi, 2012 #577) |
In supplement (Moors, 2019 #644) (Li, 2019 #745) (Gundner et al. 2019, PMID 30236861) (Gegg et al. 2012, PMID 23034917) (Choi et al. 2011, PMID). (Kurzawa-Akanbi, 2012 #577) |
(Gegg et al. 2012, PMID 23034917 but = (Kurzawa-Akanbi, 2012 #577) but = |
In supplement (Moors, 2019 #644) (Kurzawa-Akanbi, 2012 #577) ↓ | (Gegg et al. 2012, PMID 23034917 but = | ||||
| GBA+PD / CSF |
Schondorf et al. 2014, PMID 24905578) In supplement (Parnetti et al. 2017, PMID 28843015) (Huh, 2021 #2538) PPMI, ↑ (~20%) | Ask Comp Bio | |||||||
| sPD / Brain | |||||||||
| sPD / CSF | (Xicoy, 2019 #2540) 2nd, Publication available in sPD | (Xicoy, 2019 #2540) 2nd, Publication available in sPD | (Xicoy, 2019 #2540) 2nd, Publication available in sPD |
PD only / PD+ heteroz / Hetero only / GD only / PD+GD matrix
| PD only | PD+ heteroz | Hetero only | GD only | PD+GD | |
|---|---|---|---|---|---|
| 2021 Avenali phd dissertation (Huh, 2021 #2538) CSF | Fibroblast |
LIMP2, GBA activity, aSyn, gba protein, LAMP-1, Cathepsin D Fig1) in GBA+PD (n=44): GlcCer ↑ (~18%, 0.93 vs 0.79, statistically significant, huge overlap, The median GlcCer fraction in GBA+PD patients was 0.93% (IQR, 0.67-1.20) compared to 0.79% (0.59-1.04) in HC (P = 0.0001, n=227.), no difference between mild vs severe GBA mutation GlcCer. Spd: = vs HC | GlcSph: 논문x | ||
| Zama, 2009 #742) |
Fibroblast GD type not stated, ↑ GlcCer (fig 8) | ||||
| Sasagasako, 1994 #743) |
Fibroblast = GlcCer, = GlcSph (despite ↓ GBA activity) | ||||
| Leyns, 2022 #2182) Good, recent, Virginia Lee, Merck, Postmortem brain, DLB도 봄 |
In GBA+PD: ↓ GBA activity correlated with paSyn (in putamen, r=-0.26), GlcCer. = but mildly correlated with paSyn (in cingulate and frontal) GlcSph: = (gpa+pdd만 ↑) but correlated with paSyn (in putamen, r=0.42) GBA activity correlated with GlcSph (in putamen, r=-0.51) | ||||
| Moors, 2019 #644) Postmortem brain, DLB도 봄 Mol Neurobiol (2019) 56:1344-1355 |
Alterations in the activities of several other lysosomal enzymes were found in brain tissue and CSF of PD or DLB patients compared to controls, including β-hexosaminidase (β-Hex) [22-26, js: all sPD. In addition, decreased protein levels have been demonstrated for various other ALP components in the PD brain [27-30, 이중 30만 GBA+PD인데 lysosome data 없는듯,,] | ||||
|
Fig3f) =(frontal cortex, SN) – Cathepsin D mRNA: Fig3f) =(frontal cortex, SN); Fig3f) =(frontal cortex, SN) Cathepsin D activity: HC vs GBA+PD: not significant | |||||
Peripheral blood and GD studies
| Source | PD only | PD+ heteroz | Hetero only | GD only | PD+GD |
|---|---|---|---|---|---|
| PBMC GlcCer, GlcSph는 논문x | |||||
| ?, 2020 #1105) |
Dried blood spot (Perkin Elmer) GBA activity no reduction overlap! | GBA activity 대략 60% of healthy control | |||
| ?, 1997 |
PBMC (culture 아닌듯, CBE 줄때는 culture에) Type 1 GD patients (n=6) GBA activity: 10% (PBMC), monocyte도 유사결과 | ||||
| ?, 2016 |
Lymphocyte [nGD] 10-30% of control (표3), recovered by ambrosol | ||||
| ?, #2619) |
Postmortem brain, N=21, GlcCer: = GlcSph: not done | ||||
| ?, 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 | ||||
| ?, 2015 |
Fibroblast ↓ GBA activity (js 50%, this is corrected by ambroxol, fig1), slightly ↓ GBA protein (js 10%), =Prosaposin, =saposin,) =Cathepsin D |
Uncertain Spans
| location | transcription | uncertainty |
|---|---|---|
| matrix / Brain row | (Choi et al. 2011, PMID). | The PMID number is missing; the trailing ). is preserved. |
| matrix / sPD CSF | (Xicoy, 2019 #2540) placement in Cathepsin D activity / LAMP2 / LC3 columns | Three identical citations appear across three columns with the same 2nd, Publication available in sPD annotation; column placement is preserved as visible. |
| Avenali row | 2021 Avenali phd dissertation | the source label and column placement are preserved as visible; the row’s exact column boundary is unclear because the upper-left cell is partly clipped. |
| Huh fig1 row | 0.93 vs 0.79 and (P = 0.0001, n=227.) | reads as written; the n=227. token ends with a period whose role (decimal vs sentence) is ambiguous. |
| Lower postmortem rows | ?, 2020 #1105), ?, 1997, ?, 2016, ?, #2619), ?, 2019 #2553), ?, 2015 | Author names in the leftmost column are clipped or omitted (rendered as ?); EndNote-style identifiers are preserved as visible. |