{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T17:14:08Z","timestamp":1790183648535,"version":"4.1.0"},"reference-count":43,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2007,7,12]],"date-time":"2007-07-12T00:00:00Z","timestamp":1184198400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Neuroscience Research"],"published-print":{"date-parts":[[2007,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Most cellular zinc is tightly associated with metalloproteins and other Zn<jats:sup>2+<\/jats:sup>\u2010dependent proteins, which along with cellular Zn<jats:sup>2+<\/jats:sup> compartments may coordinately regulate cytoplasmic free Zn<jats:sup>2+<\/jats:sup> levels in the picomolar range. Moreover, Zn<jats:sup>2+<\/jats:sup>\u2010containing endosomes or protein complexes appear to move along axons or dendrites, suggesting a dynamic mechanism for trafficking, exchanging, or scavenging Zn<jats:sup>2+<\/jats:sup> and\/or Zn<jats:sup>2+<\/jats:sup> protein complexes in neurons. It is therefore interesting to examine whether cellular Zn<jats:sup>2+<\/jats:sup> levels might alter neurite integrity and dynamics. Here we show that membrane\u2010permeable zinc chelators, including 1,10\u2010phenanthroline, N,N,N\u2032,N\u2032\u2010tetrakis\u2010(2\u2010pyridylmethyl)\u2010ethylenediamine (TPEN), and zinquin, selectively elicit axon and dendrite degeneration but leave the cell body intact in sympathetic neurons. The process begins distally and then moves retrogradely, with a distinct \u201cdying\u2010back\u201d pattern. An inactive isomer of 1,10\u2010phenanthroline failed to cause neuite degeneration, and these chelators mediated their effects by selectively chelating Zn<jats:sup>2+<\/jats:sup>, but not other metals. Moreover, neurite degeneration was associated with a decrease in neuritic ATP levels and was caused by energy failure, because an exogenous supply of nicotinamide adenine dinucleotide (NAD) or its precursor nicotinamide suppressed the degeneration by delaying axonal ATP reduction caused by Zn<jats:sup>2+<\/jats:sup> depletion. Blockage of autophagy by 3\u2010methyladenine provided partial protection against degeneration of terminal axons or dendrites; there was, however, no obvious alteration in that of medial portions. Collectively, our results show that cellular Zn<jats:sup>2+<\/jats:sup> depletion induces a \u201cdying\u2010back\u201d degeneration characterized by an NAD\u2010 and autophagy\u2010dependent process, independently of neurite elongation dynamics. \u00a9 2007 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jnr.21411","type":"journal-article","created":{"date-parts":[[2007,7,12]],"date-time":"2007-07-12T21:22:14Z","timestamp":1184275334000},"page":"2844-2855","source":"Crossref","is-referenced-by-count":23,"title":["Cellular Zn<sup>2+<\/sup> chelators cause \u201cdying\u2010back\u201d neurite degeneration associated with energy impairment"],"prefix":"10.1002","volume":"85","author":[{"given":"Yi","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taku","family":"Kawataki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Fukui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuro","family":"Koike","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2007,7,12]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1098014"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.271.5252.1081"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200406126"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0012-1606(88)90295-3"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2005-8202"},{"key":"e_1_2_5_7_1","first-page":"659","article-title":"The \u201cdying back\u201d process. 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