A Medicinal Chemistry Perspective on Excitatory Amino Acid Transporter 2 Dysfunction in Neurodegenerative Diseases.

Autor: Fontana IC; School of Biomedical Engineering and Imaging Sciences, St Thomas' Hospital, King's College London, London SE1 7EH, United Kingdom.; Graduate Program in Biological Sciences: Biochemistry, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600, 90035-003 Porto Alegre, Brazil.; Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Blickagången 16 - Neo floor seventh, 141 83 Stockholm, Sweden., Souza DG; Graduate Program in Biological Sciences: Biochemistry, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600, 90035-003 Porto Alegre, Brazil.; Brain Institute of Rio Grande do Sul, Pontifical Catholic University of Rio Grande do Sul, Av. Ipiranga, 6681 Porto Alegre, Brazil., Souza DO; Graduate Program in Biological Sciences: Biochemistry, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600, 90035-003 Porto Alegre, Brazil.; Department of Biochemistry, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600, 90035-003 Porto Alegre, Brazil., Gee A; School of Biomedical Engineering and Imaging Sciences, St Thomas' Hospital, King's College London, London SE1 7EH, United Kingdom., Zimmer ER; Department of Biochemistry, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600, 90035-003 Porto Alegre, Brazil.; Department of Pharmacology, Universidade Federal do Rio Grande do Sul, Av. Sarmento Leite 500, sala, 90035-003 Porto Alegre, Brazil.; Graduate Program in Biological Sciences: Biochemistry (PPGBioq), and Pharmacology and Therapeutics (PPGFT), Universidade Federal do Rio Grande do Sul, Av. Sarmento Leite 500, sala, 305 Porto Alegre, Brazil.; Brain Institute of Rio Grande do Sul, Pontifical Catholic University of Rio Grande do Sul, Av. Ipiranga, 6681 Porto Alegre, Brazil.; McGill University Research Centre for Studies in Aging, McGill University, Montreal, Quebec H4H 1R3, Canada., Bongarzone S; School of Biomedical Engineering and Imaging Sciences, St Thomas' Hospital, King's College London, London SE1 7EH, United Kingdom.
Jazyk: angličtina
Zdroj: Journal of medicinal chemistry [J Med Chem] 2023 Feb 23; Vol. 66 (4), pp. 2330-2346. Date of Electronic Publication: 2023 Feb 14.
DOI: 10.1021/acs.jmedchem.2c01572
Abstrakt: The excitatory amino acid transporter 2 (EAAT2) plays a key role in the clearance and recycling of glutamate - the major excitatory neurotransmitter in the mammalian brain. EAAT2 loss/dysfunction triggers a cascade of neurodegenerative events, comprising glutamatergic excitotoxicity and neuronal death. Nevertheless, our current knowledge regarding EAAT2 in neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD), is restricted to post-mortem analysis of brain tissue and experimental models. Thus, detecting EAAT2 in the living human brain might be crucial to improve diagnosis/therapy for ALS and AD. This perspective article describes the role of EAAT2 in physio/pathological processes and provides a structure-activity relationship of EAAT2-binders, bringing two perspectives: therapy (activators) and diagnosis (molecular imaging tools).
Databáze: MEDLINE
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