| ARNWG | https://mytakeda.sharepoint.com/sites/Age-RelatedNeurodegenerationWorkingGroup/Shared%20Documents/Forms/AllItems.aspx?RootFolder=/sites%2FAge-RelatedNeurodegenerationWorkingGroup%2FShared%20Documents%2FPresentations&View=%7B2EB2788D-DB50-4A88-AB86-FE190DA3F540%7D |
| team site of Neuroscience DDU. | https://mytakeda.sharepoint.com/teams/NeuroscienceDDU |
| NSRB | https://mytakeda.sharepoint.com/sites/NSTA/SitePages/NSRB.aspx |
| sDIB | https://mytakeda.sharepoint.com/teams/NeuroscienceDDU/Shared%20Documents/Forms/AllItems.aspx?newTargetListUrl=%2Fteams%2FNeuroscienceDDU%2FShared%20Documents&viewpath=%2Fteams%2FNeuroscienceDDU%2FShared%20Documents%2FForms%2FAllItems%2Easpx&viewid=2e9804a9%2D1b86%2D496a%2Da4cc%2D176748806298&id=%2Fteams%2FNeuroscienceDDU%2FShared%20Documents%2FScientific%20DIB%20review |
| PRF (Pipeline Review Forum) |
https://mytakeda.sharepoint.com/sites/NSTA/SitePages/Portfolio-Review-Forum.aspx (old) https://mytakeda.sharepoint.com/teams/NeuroscienceDDU/Shared%20Documents/Forms/AllItems.aspx?newTargetListUrl=%2Fteams%2FNeuroscienceDDU%2FShared%20Documents&viewpath=%2Fteams%2FNeuroscienceDDU%2FShared%20Documents%2FForms%2FAllItems%2Easpx&viewid=2e9804a9%2D1b86%2D496a%2Da4cc%2D176748806298&id=%2Fteams%2FNeuroscienceDDU%2FShared%20Documents%2FNS%20TAU%20Pipeline%20Review%20Forum |
| Consortia | https://mytakeda.sharepoint.com/teams/tamo/NeuroscienceTAU/Business%20Ops/Forms/AllItems.aspx?viewid=200e2033%2D44db%2D4515%2Da9c5%2D994883ae35e4&id=%2Fteams%2Ftamo%2FNeuroscienceTAU%2FBusiness%20Ops%2FConsortia |
| Neuroscience cross-department workshop | https://mytakeda.sharepoint.com/teams/NeuroscienceDDU/Shared%20Documents/Forms/AllItems.aspx?csf=1&e=uyvbl3&cid=7359f474%2D3721%2D44dc%2Dab66%2D81d5e1c180f4&RootFolder=%2Fteams%2FNeuroscienceDDU%2FShared%20Documents%2FNeuroscience%20Japan%20cross%20department%20workshop%2F2020%2D02%2D19%201st%20workshop&FolderCTID=0x012000BDA41FA7831FF94B9A545C7122F1B295 |
| Biomarker One-Pager (NSTM) | https://mytakeda.sharepoint.com/sites/NSTM/Biomarker%20OnePagers/Forms/AllItems.aspx |
| Biomarker Tracker (NSTM) | https://mytakeda.sharepoint.com/:x:/r/sites/NSTM/_layouts/15/Doc.aspx?sourcedoc=%7B78D96078-74EB-4A57-87C2-9B3028A5C7F4%7D&file=000%20NSTM%20BMx%20One-Pager%20Tracker_2019-11-11.xlsx&action=default&mobileredirect=true |
| Kamiguchi san's group | https://mytakeda.sharepoint.com/:x:/r/sites/NST/_layouts/15/Doc.aspx?sourcedoc=%7B76570AE7-104E-482F-8152-17A99E69A2F3%7D&file=01_Study%20List.xlsx&action=default&mobileredirect=true&cid=0f9667ac-f1ba-412c-9a82-e07a740429d3 |
| NLRP3i (이미 old) | https://mytakeda.sharepoint.com/sites/InterACT-RAD-Pipeline/NLRP3%20Inhibitor/site%20pages/homepage.aspx |
| |
| BioOrchestra | https://mytakeda.sharepoint.com/teams/site021-2/takedaglobal/grmind/GRI/CNS/RICI/1-Partnership/Shared%20Documents/Forms/AllItems.aspx?e=5%3A457681ef0bc248b0a981754cc589bb31&at=9&RootFolder=%2Fteams%2Fsite021%2D2%2Ftakedaglobal%2Fgrmind%2FGRI%2FCNS%2FRICI%2F1%2DPartnership%2FShared%20Documents%2FFolder%20for%20materials%20to%20share%20with%20other%20persons%2Fbiorchestra&FolderCTID=0x0120000B4B7FD5E4B2EC40B014E5B9C663BB68 |
| NSTA | https://mytakeda.sharepoint.com/sites/NSTA |
| RSLT 202004 | https://mytakeda.sharepoint.com/teams/NeuroscienceDDU/Shared%20Documents/Forms/AllItems.aspx?csf=1&web=1&e=NgSvUY&cid=52b2ff3c%2Dce5b%2D462c%2D90e5%2D4d206cd32865&RootFolder=%2Fteams%2FNeuroscienceDDU%2FShared%20Documents%2FRSLT%20review%2F20200421&FolderCTID=0x012000BDA41FA7831FF94B9A545C7122F1B295 |
| CNS | https://mytakeda.sharepoint.com/teams/TCAL/Departments/CNS/default.aspx?e=1%3Ad25033b0edc74ef7bac2311b82e3bac5 |
| 원천징수영수증 | Income Tax Withholding Statement https://urldefense.com/v3/__https://takeda-cws.company.works-hi.com/self-workflow/cws/cws?@SID=null&@SUB=root.cws.hr_personal&@SN=root.cws_;!!KDurfCY!saVe1WmXQVz-P5obys6MAbEvX01cB0-xu7zmt8jzOgdAchNzBNsDfPvJBKvYUcIcAw$ |
| GPT playbook | https://mytakeda.sharepoint.com/sites/Central-PMO/Shared%20Documents/Forms/AllItems.aspx?id=%2Fsites%2FCentral%2DPMO%2FShared%20Documents%2FEnterprise%20GPT%20Playbook%5FvFINAL%2Epdf&parent=%2Fsites%2FCentral%2DPMO%2FShared%20Documents%2FEnterprise%20GPT%20Playbook |
Shipment
| Narita airport Nanka Express | Yamato onu | BW3F-20 | Matsui Hideki | Where? | |
|---|---|---|---|---|---|
| The person receive | Allocate slot (tank no, slot no) | Transfer to central LN tanks |
Sigma-1 Receptor (σ1R)
- a chaperone protein
- Mechanism
Fundamental Functions of Sig-1R (SIGMAR1) on ER Stress Regulation in Neurodegenerative Disorders
① Misfolded proteins increasing with age induce ER stress and modification in calcium homeostasis
② Calcium depletion in ER activates Sig-1R, which separates from BiP
Pathway a: IP3R and ATP Production
③a: Sig-1R interacts with IP3R and allows ankyrin to be detached from IP3R, which stabilize and enhance opening of IP3R
④a: Calcium ions efflux from ER lumen into mitochondria through IP3R, VDAC, and MCU
⑤a: Calcium ions increase in mitochondria enhances ATP production through TCA cycle and oxidative phosphorylation
Pathway b: Unfolded Protein Response (UPR)
③b: Sig-1R interacts with IRE1
④b: Activated IRE1 acts as an endonuclease and is able to cut an intron from xbp1 to allow its translation
⑤b: XBP1 allows the transcription of ER chaperone genes and pro-survival genes
Cody S, Goguadze N, Yasui Y, Kimura Y, Wang SM, Shankadze N, Wu HE, Su TP. Knocking Out Sigma-1 Receptors Reveals Diverse Health Problems. Cell Mol Neurobiol. 2020 Oct 23. doi: 10.1007/s10571-020-00983-3. Epub ahead of print. PMID: 33095392. ATP: adenosine triphosphate; BiP: binding immunoglobulin protein; ER: endoplasmic reticulum; ERAD: endoplasmic-reticulum-associated protein degradation; IP3R: inositol trisphosphate receptor; IRE1: inositol-requiring enzyme 1; MCU: mitochondrial calcium uniporter; OxPhos: oxidative phosphorylation; TCA: tricarboxylic acid cycle; VDAC: voltage-dependent anion channel; XBP1: X-box binding protein 1; xbp1s: xbp1 mRNA spliced; xbp1u: xbp1 mRNA unspliced.
σ1R PET
| Study | |||
|---|---|---|---|
| C-SA-4503 | (11C-labeled 1-[2-(3,4-dimethoxyphenthyl)]-4-(3-phenylpropyl)-piperazine dihydrochloride | (Mansur, 2018 #876) | HV |
| MIND-MAP | sPD | ||
| 3F-FTC-146 | ANAVEX®2-73 (blarcamesine | Mouse, TO study |
SILK
(Stable Isotope Labeling Kinetics)
- reported in Sato et al (2018) Neuron — tau kinetics in iPSC-derived neuron cultures
- aSyn — biomarkers relevant to
- ?? — what are the readouts? What are benefits compared to just looking at aSyn level in the lysates or supernatant
- application: kinetics, aSyn turnover vs aSyn degradation (Protak) vs aggregate formation
- they have a company called C2N Diagnostics (http://www.c2ndiagnostics.com/) that provides SILK as a service to pharma for a variety of biomarkers relevant to Alzheimer’s disease and ALS (see the list here: http://www.c2ndiagnostics.com/our-products/biomarker-assays/).
- C2N does not currently have a marketed assay for alpha-syn
- Paul Kotzbauer has NIH grants to work on this.
Communi[ty]
| What natural history data are you aware of that is tracking GBA patients longitudinally? What data and samples are they collecting (cognition, imaging, plasma samples?) | Groups looking at progression: PPMI (richest), Columbia (Roy N. Alcalay). Cambridge (The Barker/Williams-Gray Lab: Roger A Barker, Caroline H Williams-Gray, Thomas Stoker seems a junior) | |
| lysosome | What may be the role of lysosomal markers (eg. CSF) as pharmacodynamic biomarkers and potentially for patient stratification for GBA-directed treatment? | Time course of lysosomal marker change? |
| How can we develop robust lysosomal markers? | Association with protein degradation | |
| rs | CSF sample from PPMI | Large genotyping: Parkinson Foundation genotyping, MJF, Ro-Pat study (centigene genotyping |
| early | Advanced | |
|---|---|---|
| DatScan | Not suitable due/to floor effect | |
| ↑ AE | ||
| Desperate and willing to accept an invasive Tx | ||
| ↑ non-motor symptoms (eg. Cognition, ie |
Uncertain Spans
- Many of the SharePoint URLs are extremely long and word-wrap mid-token in the source layout; the URLs are reproduced as a single contiguous string per row but exact token boundaries (especially around ”?”, ”&” and “%2D” segments) could not be visually verified at this resolution.
- The shipment table column header “Yamato onu” is reproduced as printed; “onu” may be a truncation or typographical variant of a courier name and was not corrected.
- The Sigma-1R review citation block is reproduced as a continuous italic caption; the abbreviation list at the bottom of the figure was partly clipped at the right edge (“xbp1u: xbp1 mRNA unspliced”), and any further abbreviations beyond that are not visible on this photo.
- The leftmost column of the “Communi[ty]” table is partly clipped under the table border — some row labels visible only as fragments (“lysosome”, “rs”) are reproduced as printed without inferring the full label.
- The header label of the second-to-last bottom table is “early / Advanced” only; whether a third intermediate-stage column existed in the source is not determinable from this photo.