{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T17:06:43Z","timestamp":1777396003360,"version":"3.51.4"},"reference-count":41,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2019,12,7]],"date-time":"2019-12-07T00:00:00Z","timestamp":1575676800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2020,1,21]]},"abstract":"<jats:p>Alzheimer\u2019s disease (AD) represents a major public health threat and, unfortunately, available therapeutics provide only temporary symptomatic relief. AD is a complex multifactorial disease and failure of single target therapeutics targeting amyloid-\u03b2 (A\u03b2) in recent clinical trials suggests that future AD drug development should be focused on simultaneous targeting of several pathological hallmarks of the disease. Recently, we have shown that GMP-1, a 2-(methoxymethyl)pyrimido [1,\u00a02- a] benzimidazol-4-ol, protects mitochondrial function in drosophila and mice models of AD, and improved memory and behavior indicating neuroprotective effect of GMP-1 treatment. Here, we have found that GMP-1 specifically binds to copper and zinc, metals that are dysregulated in AD brain. Addition of GMP-1 does not inhibit metal-dependent enzymatic reactions. Also, binding of Zn(II) and Cu(II) by GMP-1 is weaker than the 8-hydroxyquinoline scaffold compound clioquinol previously tested in AD clinical trials. However, GMP-1 affects Cu(II)-dependent A\u03b2 fibrillization as well as oxidative damage and viability of SH-SY5Y cells upon addition of Cu(II) and A\u03b2. Our data provide new insight on GMP-1 as a Zn(II) and Cu(II) specific metal chelator of moderate affinity that can be responsible for some of its neuroprotective effects observed in AD animal models.<\/jats:p>","DOI":"10.3233\/jad-190695","type":"journal-article","created":{"date-parts":[[2019,12,13]],"date-time":"2019-12-13T13:18:27Z","timestamp":1576243107000},"page":"695-705","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":9,"title":["Metal Binding by GMP-1 and Its Pyrimido [1, 2]benzimidazole Analogs Confirms Protection Against Amyloid-\u03b2 Associated Neurotoxicity"],"prefix":"10.1177","volume":"73","author":[{"given":"Rajnish","family":"Kumar","sequence":"first","affiliation":[{"name":"Department of Neurobiology, Care sciences and Societ, Centre for Alzheimer Research, Division of Neurogeriatrics, Karolinska Institutet, Solna, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pavel 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