Computer-Aided Drug Design Approaches to Study Key Therapeutic Targets in Alzheimer’s Disease

Part of the Neuromethods book series (NM, volume 132)


Alzheimer’s Disease (AD) is one of the most common and complex age-related neurodegenerative disorders in elderly people. Currently there is no cure for AD, and available therapeutic alternatives only improve both cognitive and behavioral functions. For that reason, the search for anti-AD therapeutic agents with neuroprotective properties is highly demanding. Several research studies have implicated the involvement of G-Protein-Coupled Receptors (GPCRs) in diverse neurotransmitter systems that are dysregulated in AD, mainly in modulation of amyloidogenic processing of Amyloid Precursor Protein (APP) and of microtubule-associated protein tau phosphorylation and in learning and memory activities in in vivo AD models subjected to numerous behavioral procedures. In this chapter, a special focus will be given to the structure- and ligand-based in silico approaches and their applicability on the development of small molecules that target various GPCRs potentially involved in AD such as 5-hydroxytryptamine receptors, adenosine receptors, adrenergic receptors, chemokine receptors, histamine receptors, metabotropic glutamate receptors, muscarinic acetylcholine receptors, and opioid receptors.

Key words

Alzheimer’s disease GPCRs G-proteins Drug design Docking Pharmacophore QSAR 


Acknowledgments and Funding

This work had the financial support of Fundação para a Ciência e a Tecnologia (FCT/MEC) through national funds and cofinanced by FEDER, under the Partnership Agreement PT2020 (projects UID/QUI/50006/2013 and POCI/01/0145/FEDER/007265). Irina S. Moreira acknowledges support by the FCT – Investigator Programme – IF/00578/2014 (cofinanced by European Social Fund and Programa Operacional Potencial Humano), a Marie Skłodowska-Curie Individual Fellowship MSCA-IF-2015 [MEMBRANEPROT 659826]. This work was also financed by the European Regional Development Fund (ERDF), through the Centro 2020 Regional Operational Programme under project CENTRO-01-0145-FEDER-000008, BrainHealth 2020, and through the COMPETE 2020 – Operational Programme for Competitiveness and Internationalisation and Portuguese national funds via FCT, under project POCI-01-0145-FEDER-007440. Rita Melo acknowledges support from the FCT (SFRH/BPD/97650/2013 and UID/Multi/04349/2013 project). MNDSC further acknowledges FCT for the sabbatical grant SFRH/BSAB/127789/2016.


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Copyright information

© Springer Science+Business Media LLC 2018

Authors and Affiliations

  1. 1.LAQV@REQUIMTE, Department of Chemistry and Biochemistry, Faculty of SciencesUniversity of PortoPortoPortugal
  2. 2.GIGA Cyclotron Research Centre In Vivo ImagingUniversity of LiègeLiègeBelgium
  3. 3.CNC – Center for Neuroscience and Cell BiologyFaculty of Medicine, University of CoimbraCoimbraPortugal
  4. 4.Center for Nuclear Sciences and TechnologiesInstituto Superior Técnico, University of LisbonBobadela LRSPortugal
  5. 5.Bijvoet Center for Biomolecular ResearchFaculty of Science - Chemistry, Utrecht UniversityUtrechtThe Netherlands
  6. 6.(MNDSC) LAQV@REQUIMTE/Department of Chemistry and BiochemistryUniversity of PortoPortoPortugal
  7. 7.(ISM) CNC – Center for Neuroscience and Cell BiologyFaculty of Medicine, University of CoimbraCoimbraPortugal

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