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The lipophilic metal chelators DP\u2010109 and DP\u2010460 which chelate calcium, copper, and zinc were tested in the G93A\u2010transgenic ALS mouse model. Both compounds significantly extended survival, DP\u2010109 (5\u2003mg\/kg\/day) by 10%, DP\u2010460 (10\u2003mg\/kg\/day) by 9%. While the effect on survival was relatively small, chelator treatment also improved motor performance, dramatically reduced cell loss in the lumbar spinal cord and decreased reactive astrocytosis and microgliosis. Markers of oxidative damage, tumor necrosis factor (TNF)\u2010\u03b1and \u03b1\u2010synuclein were reduced in the lumbar spinal cord of G93A mice treated with DP\u2010109 or DP\u2010460 as compared with vehicle\u2010treated animals. Furthermore, the treatment induced protein expression of the transcription factor hypoxia inducible factor\u20101\u03b1 and mRNA levels of vascular endothelial growth factor as a corresponding target gene. In line with previous studies using metal chelators in the G93A animal model, our results suggest that these compounds have neuroprotective capacities in ALS.<\/jats:p>","DOI":"10.1111\/j.1471-4159.2007.04604.x","type":"journal-article","created":{"date-parts":[[2007,5,7]],"date-time":"2007-05-07T13:41:54Z","timestamp":1178545314000},"page":"991-1000","source":"Crossref","is-referenced-by-count":50,"title":["The lipophilic metal chelators DP\u2010109 and DP\u2010460 are neuroprotective in a transgenic mouse model of amyotrophic lateral sclerosis"],"prefix":"10.1111","volume":"102","author":[{"given":"Susanne","family":"Petri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noel Y.","family":"Calingasan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osama A.","family":"Alsaied","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Wille","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmoud","family":"Kiaei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan E.","family":"Friedman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oxana","family":"Baranova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan C.","family":"Chavez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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