{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T22:29:43Z","timestamp":1768343383886,"version":"3.49.0"},"reference-count":40,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2006,6,12]],"date-time":"2006-06-12T00:00:00Z","timestamp":1150070400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2006,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>\u03b2 Amyloid protein (A\u03b2) and acetylcholinesterase (AChE) have been shown to be closely implicated in the pathogenesis of Alzheimer's disease. In the current study, we investigated the effects of bis(7)\u2010tacrine, a novel dimeric AChE inhibitor, on A\u03b2\u2010induced neurotoxicity in primary cortical neurons. Bis(7)\u2010tacrine, but not other AChE inhibitors, elicited a marked reduction of both fibrillar and soluble oligomeric forms of A\u03b2\u2010induced apoptosis as evidenced by chromatin condensation and DNA specific fragmentation. Both nicotinic and muscarinic receptor antagonists failed to block the effects of bis(7)\u2010tacrine. Instead, nimodipine, a blocker of L\u2010type voltage\u2010dependent Ca<jats:sup>2+<\/jats:sup> channels (VDCCs), attenuated A\u03b2 neurotoxicity, whereas N\u2010, P\/Q\u2010 or R\u2010type VDCCs blockers and ionotropic glutamate receptor antagonists did not. Fluorescence Ca<jats:sup>2+<\/jats:sup> imaging assay revealed that, similar to nimodipine, bis(7)\u2010tacrine reversed A\u03b2\u2010triggered intracellular Ca<jats:sup>2+<\/jats:sup> increase, which was mainly contributed by the extracellular Ca<jats:sup>2+<\/jats:sup> instead of endoplasmic reticulum and mitochondria Ca<jats:sup>2+<\/jats:sup>. Concurrently, using whole cell patch\u2010clamping technique, it was found that bis(7)\u2010tacrine significantly reduced the augmentation of high voltage\u2010activated inward calcium currents induced by A\u03b2. These results suggest that bis(7)\u2010tacrine attenuates A\u03b2\u2010induced neuronal apoptosis by regulating L\u2010type VDCCs, offers a novel modality as to how the agent exerts neuroprotective effects.<\/jats:p>","DOI":"10.1111\/j.1471-4159.2006.03960.x","type":"journal-article","created":{"date-parts":[[2006,6,12]],"date-time":"2006-06-12T11:44:12Z","timestamp":1150112652000},"page":"1400-1410","source":"Crossref","is-referenced-by-count":89,"title":["Bis(7)\u2010tacrine attenuates \u03b2 amyloid\u2010induced neuronal apoptosis by regulating L\u2010type calcium channels"],"prefix":"10.1111","volume":"98","author":[{"given":"Hongjun","family":"Fu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenming","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanzhi","family":"Lao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jialie","family":"Luo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nelson T. 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