Alzheimer disease
GtoPdb Disease Summaries
This section gives an overview of the disease, and where available shows the following:
- Synonyms: Shows known synonyms for the disease.
- Description: Gives a basic description/definition of the disease.
- Database Link: External links to the same disease at the Disease Ontology, OMIM or Orphanet sites.
- Immunopharmacology comments: General comments about the target's role in immunopharmacology, provided by GtoImmuPdb curators.
- Associated with: Counts are displayed for the total targets the disease is associated with in GtoPdb. The counts of targets and ligands of immunological relevance associated to the disease are also shown.
More information can be found in the help pages.
✖| Disease ID: | 56 | |
| Name: | Alzheimer disease | |
| Associated with: | 8 targets | |
Targets
GtoPdb Disease Summaries - Targets
Click on the target name to link to its detailed view page
Where available, information is display on the role of the target in the disease; drugs which target the disease and their therapeutic use and side-effects.
If there is mutation data curated in GtoPdb this is indicated, with a link back to the appropriate section on the target detailed view page
Immuno ligand interactions - If available, a table of immuno-relevant ligands is shown. These ligands have been curated as having an association to the disease and possess interaction data with the target in GtoPdb. The approval status of the ligand is shown, along with curator comments and an indication of whether the target is considered the primary target of the ligand.
More information can be found in the help pages.
✖| C5a1 receptor | |
| Comments: | C5aR colocalises to microglia in amyloid plaques in the Tg2576 and hAPP mouse models of Alzheimer's disease. Inhbition of C5aR, through oral administration of PMX205, in these models reduces pathology and results in improved behavioural responses. |
| References: | 1,6 |
| GPR3 | |
| Role: | Research has shown that GPR3 modulates amyloid-beta peptide generation in neurons and may be a potential therapeutic target for the treatment of Alzheimer's disease |
| References: | 12 |
| FZD5 | |
| References: | 8 |
| KCa2.2 | |
| Role: | Intrathecal apamin injection increases learning and memory responses in mice and rats and KCa2.2 overexpression impairs learning and memory. |
| Drugs: | Apamin (experimentally in rodents) |
| Side effects: | High doses of apamin induce seizures and lead to Purkinje cell degeneration in the cerebellum. |
| Therapeutic use: | KCa2,2 blockers have been suggested as memory enhancers. |
| References: | 3-5,7,9-11,13 |
| NLRP1 |
| NLRP3 |
| programmed cell death 1 (CD279) | |
| Role: | In mouse models of Alzheimer's disease anti-PD1 antibody treatment was used to induce immune checkpoint blockade. The biological response included an interferon (IFN)-γ-dependent systemic immune and recruitment of monocyte-derived macrophages to the brain, which was associated amyloid beta plaque clearance and improved cognitive function. These results point to immune checkpoints as valid targets for therapeutic intervention in Alzheimer's disease. |
| References: | 2 |
| myeloperoxidase |
Ligands
GtoPdb Disease Summaries - Ligands
Click ligand name to view ligand summary page
- Approved: If the ligand is an approved drug this is indicated, along with approval bodies.
- Immuno: Immuno icon indicates the ligand is immuno-relevant
Click the arrow in the final column to expand comments
- Immuno Disease Comments: Curatorial comments specifically added as part of GtoImmuPdb. They give more information on the association between the ligand and disease in the context of immunopharmacology.
- Clinical Use: General clinical comments relating to the ligand and may not necessarily be specific to the disease in question. With hyperlink to more details on the ligand summary pages.
- Bioactivty Comments: Curatorial comments specifically about the compounds biological activity - with hyperlink to more details on the ligand summary pages.
More information can be found in the help pages.
✖No ligand related data available for Alzheimer disease
References
1. Ager RR, Fonseca MI, Chu SH, Sanderson SD, Taylor SM, Woodruff TM, Tenner AJ. (2010) Microglial C5aR (CD88) expression correlates with amyloid-beta deposition in murine models of Alzheimer's disease. J Neurochem, 113 (2): 389-401. [PMID:20132482]
2. Baruch K, Deczkowska A, Rosenzweig N, Tsitsou-Kampeli A, Sharif AM, Matcovitch-Natan O, Kertser A, David E, Amit I, Schwartz M. (2016) PD-1 immune checkpoint blockade reduces pathology and improves memory in mouse models of Alzheimer's disease. Nat Med, 22 (2): 135-7. [PMID:26779813]
3. Blank T, Nijholt I, Kye MJ, Spiess J. (2004) Small conductance Ca2+-activated K+ channels as targets of CNS drug development. Curr Drug Targets CNS Neurol Disord, 3 (3): 161-7. [PMID:15180477]
4. Deschaux O, Bizot JC. (2005) Apamin produces selective improvements of learning in rats. Neurosci Lett, 386 (1): 5-8. [PMID:15985330]
5. Deschaux O, Bizot JC, Goyffon M. (1997) Apamin improves learning in an object recognition task in rats. Neurosci Lett, 222 (3): 159-62. [PMID:9148239]
6. Fonseca MI, Ager RR, Chu SH, Yazan O, Sanderson SD, LaFerla FM, Taylor SM, Woodruff TM, Tenner AJ. (2009) Treatment with a C5aR antagonist decreases pathology and enhances behavioral performance in murine models of Alzheimer's disease. J Immunol, 183 (2): 1375-83. [PMID:19561098]
7. Hammond RS, Bond CT, Strassmaier T, Ngo-Anh TJ, Adelman JP, Maylie J, Stackman RW. (2006) Small-conductance Ca2+-activated K+ channel type 2 (SK2) modulates hippocampal learning, memory, and synaptic plasticity. J Neurosci, 26 (6): 1844-53. [PMID:16467533]
8. Li B, Zhong L, Yang X, Andersson T, Huang M, Tang SJ. (2011) WNT5A signaling contributes to Aβ-induced neuroinflammation and neurotoxicity. PLoS ONE, 6 (8): e22920. [PMID:21857966]
9. Messier C, Mourre C, Bontempi B, Sif J, Lazdunski M, Destrade C. (1991) Effect of apamin, a toxin that inhibits Ca(2+)-dependent K+ channels, on learning and memory processes. Brain Res, 551 (1-2): 322-6. [PMID:1913161]
10. Mourre C, Fournier C, Soumireu-Mourat B. (1997) Apamin, a blocker of the calcium-activated potassium channel, induces neurodegeneration of Purkinje cells exclusively. Brain Res, 778 (2): 405-8. [PMID:9459560]
11. Stackman RW, Hammond RS, Linardatos E, Gerlach A, Maylie J, Adelman JP, Tzounopoulos T. (2002) Small conductance Ca2+-activated K+ channels modulate synaptic plasticity and memory encoding. J Neurosci, 22 (23): 10163-71. [PMID:12451117]
12. Thathiah A, Spittaels K, Hoffmann M, Staes M, Cohen A, Horré K, Vanbrabant M, Coun F, Baekelandt V, Delacourte A, Fischer DF, Pollet D, De Strooper B, Merchiers P. (2009) The orphan G protein-coupled receptor 3 modulates amyloid-beta peptide generation in neurons. Science, 323: 946-951. [PMID:19213921]
13. Wulff H, Kolski-Andreaco A, Sankaranarayanan A, Sabatier JM, Shakkottai V. (2007) Modulators of small- and intermediate-conductance calcium-activated potassium channels and their therapeutic indications. Curr Med Chem, 14 (13): 1437-57. [PMID:17584055]
