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Alzheimer disease

Disease ID:56
Name:Alzheimer disease
Associated with:8 targets
Alzheimer's disease
Database Links
Disease Ontology: DOID:10652
OMIM: 104300


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
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
References:  8
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
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


No ligand related data available for Alzheimer disease


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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]