The role of G protein-coupled receptors in the pathology of Alzheimer's disease
Abstract
G protein-coupled receptors (GPCRs) are involved in numerous key neurotransmitter systems in the brain that are disrupted in Alzheimer's disease (AD). GPCRs also directly influence the amyloid cascade through modulation of the α-, β- and γ-secretases, proteolysis of the amyloid precursor protein (APP), and regulation of amyloid-β degradation. Additionally, amyloid-β has been shown to perturb GPCR function. Emerging insights into the mechanistic link between GPCRs and AD highlight the potential of this class of receptors as a therapeutic target for AD.
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GPR20 belongs to the family of the G-protein-coupled receptors, which participate in intracellular second messenger systems triggered by different hormones and neurotransmitters, and amyloid β.
“GPR20 belongs to the family of the G-protein-coupled receptors, which participate in intracellular second messenger systems triggered by different hormones and neurotransmitters, and amyloid β.53, 54, 55”
From APOE*E2 allele delays age of onset in PSEN1 E280A Alzheimer’s disease (2016) · cites this paper as [55]
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Phillips, T., Barnes, A., Scott, S., et al. (1998) · Neuroreport · doi:10.1097/00001756-199807130-00034 · Cited by 17 · see citing works
Horgan, J., Miguel-Hidalgo, J. J., Thrasher, M., & Bissette, G. (2007) · Journal of Alzheimer s Disease · doi:10.3233/jad-2007-12201 · Cited by 17 · see citing works
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Masters, C. L., Bateman, R., Blennow, K., Rowe, C. C., Sperling, R. A., & Cummings, J. L. (2015) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2015.56 · Cited by 1,853 · see citing works
Microglial Aβ Receptors in Alzheimer’s Disease
Yu, Y., & Ye, R. D. (2015) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-014-0101-6 · Cited by 247 · see citing works
APOE*E2 allele delays age of onset in PSEN1 E280A Alzheimer’s disease
Vélez, J. I., Lopera, F., Sepulveda-Falla, D., Patel, H. R., Johar, A. S., Chuah, A., Tobón, C., Rivera, D., Villegas, A., Cai, Y., et al. (2016) · Molecular Psychiatry · doi:10.1038/mp.2015.177 · Cited by 111 · see citing works
Desale, S. E., Chidambaram, H., & Chinnathambi, S. (2021) · Molecular Biomedicine · doi:10.1186/s43556-021-00036-1 · Cited by 99 · see citing works
Olajide, O. J., Yawson, E. O., Gbadamosi, I. T., Arogundade, T. T., Lambe, E., Obasi, K., Lawal, I. T., Ibrahim, A., & Ogunrinola, K. Y. (2017) · Environmental Toxicology and Pharmacology · doi:10.1016/j.etap.2017.02.010 · Cited by 79 · see citing works
Fine Tuning Muscarinic Acetylcholine Receptor Signaling Through Allostery and Bias
van der Westhuizen, E. T., Choy, K. H. C., Valant, C., McKenzie-Nickson, S., Bradley, S. J., Tobin, A. B., Sexton, P. M., & Christopoulos, A. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.606656 · Cited by 63 · see citing works
Adewale, Q., Khan, A. F., Carbonell, F., Iturria-Medina, Y., & Initiative, A. D. N. (2021) · eLife · doi:10.7554/elife.62589 · Cited by 44 · see citing works
Distinct sex-specific DNA methylation differences in Alzheimer’s disease
C. Silva, T., Zhang, W., Young, J. I., Gomez, L., Schmidt, M. A., Varma, A., Chen, X. S., Martin, E. R., & Wang, L. (2022) · Alzheimer's Research & Therapy · doi:10.1186/s13195-022-01070-z · Cited by 33 · see citing works
“Previously, GPCRs have been implicated in the pathogenesis of Alzheimer’s disease (AD) by multiple studies [83, 84].”
BackgroundBeta-amyloid short- and long-term synaptic entanglement
Lanni, C., Fagiani, F., Racchi, M., Preda, S., Pascale, A., Grilli, M., Allegri, N., & Govoni, S. (2019) · Pharmacological Research · doi:10.1016/j.phrs.2018.11.018 · Cited by 29 · see citing works
Mutations modifying sporadic Alzheimer’s disease age of onset
Vélez, J. I., Lopera, F., Patel, H. R., Johar, A. S., Cai, Y., Rivera, D., Tobón, C., Villegas, A., Sepulveda‐Falla, D., Lehmann, S. G., et al. (2016) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32493 · Cited by 19 · see citing works
GPR75: an exciting new target in metabolic syndrome and related disorders
Murtaza, B., Asghar, F., & Patoli, D. (2022) · Biochimie · doi:10.1016/j.biochi.2022.01.005 · Cited by 18 · see citing works
- Authors
- Thathiah, A., & De Strooper, B.
- Affiliations
- Vlaams Instituut voor Biotechnologie (BE)
- Corresponding author
- Thathiah, Amantha
- ORCID
- Thathiah, Amantha
- Venue
- Nature Reviews Neuroscience
- Published
- 2011-01-20
- Volume
- 12
- Issue
- 2
- Pages
- 73-87
- ISSN
- 1471-003X (ISSN-L)
- 1471-0048
- OpenAlex
- W2077225773
- Cited by
- 288
- References
- 199
- Citations by year
- 2026: 6 · 2025: 17 · 2024: 13 · 2023: 11 · 2022: 21 · 2021: 17 · 2020: 21 · 2019: 20 · 2018: 23 · 2017: 24 · 2016: 25 · 2015: 23 · 2014: 13 · 2013: 23 · 2012: 17
- FWCI
- 2.30
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature reviews. Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Lirias (KU Leuven) (submittedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- G protein-coupled receptors, Alzheimer's disease, amyloid-beta, amyloid hypothesis, secretases, amyloid precursor protein, amyloid beta degradation, neurotransmitter systems, therapeutic target, multi-target therapy
- MeSH terms
- Alzheimer Disease, Animals, Brain, Humans, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Neurotransmitter Agents, Receptors, G-Protein-Coupled, Amyloid Precursor Protein Secretases
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