{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T23:57:58Z","timestamp":1790207878975,"version":"4.1.0"},"reference-count":52,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"855","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Signal."],"published-print":{"date-parts":[[2024,9,24]]},"abstract":"<jats:p>\n            Basal forebrain cholinergic neurons (BFCNs) extend long projections to multiple regions in the brain to regulate cognitive functions. Degeneration of BFCNs is seen with aging, after brain injury, and in neurodegenerative disorders. An increase in the amount of the immature proform of nerve growth factor (proNGF) in the cerebral cortex results in retrograde degeneration of BFCNs through activation of proNGF receptor p75\n            <jats:sup>NTR<\/jats:sup>\n            . Here, we investigated the signaling cascades initiated at the axon terminal that mediate proNGF-induced retrograde degeneration. We found that local axonal protein synthesis and retrograde transport mediated proNGF-induced degeneration initiated from the axon terminal. Analysis of the nascent axonal proteome revealed that proNGF stimulation of axonal terminals triggered the synthesis of numerous proteins within the axon, and pathway analysis showed that amyloid precursor protein (APP) was a key upstream regulator in cultured BFCNs and in mice. Our findings reveal a functional role for APP in mediating BFCN axonal degeneration and cell death induced by proNGF.\n          <\/jats:p>","DOI":"10.1126\/scisignal.adn2616","type":"journal-article","created":{"date-parts":[[2024,9,24]],"date-time":"2024-09-24T17:58:17Z","timestamp":1727200697000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":6,"title":["ProNGF elicits retrograde axonal degeneration of basal forebrain neurons through p75\n            <sup>NTR<\/sup>\n            and induction of amyloid precursor protein"],"prefix":"10.1126","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-5926-5116","authenticated-orcid":true,"given":"Srestha","family":"Dasgupta","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, Rutgers University, Newark, NJ 07102, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mansi A.","family":"Pandya","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Rutgers University, Newark, NJ 07102, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6216-0101","authenticated-orcid":true,"given":"Juan P.","family":"Zanin","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Rutgers University, Newark, NJ 07102, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Liu","sequence":"additional","affiliation":[{"name":"New Jersey Medical School, Medical Science Building, 185 South Orange Avenue, Newark, NJ 07103, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Sun","sequence":"additional","affiliation":[{"name":"New Jersey Medical School, Medical Science Building, 185 South Orange Avenue, Newark, NJ 07103, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5731-5335","authenticated-orcid":true,"given":"Hong","family":"Li","sequence":"additional","affiliation":[{"name":"New Jersey Medical School, Medical Science Building, 185 South Orange Avenue, Newark, NJ 07103, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3638-3504","authenticated-orcid":true,"given":"Wilma J.","family":"Friedman","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Rutgers University, Newark, NJ 07102, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2016.09.006"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7058341"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2006.09.002"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep13158"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2687-10.2010"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(95)00357-V"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(90)90166-D"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.1993.1007"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(85)90163-0"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.3798108"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature02319"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1560-06.2006"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.3109\/02699052.2015.1088963"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aww074"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1177\/1759091420930865"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0067-23.2023"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2019.00431"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3609"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1867-19.2019"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M010548200"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M205167200"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnint.2021.689208"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0162-22.2022"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6123(08)63270-7"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1105681"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-20-07644.1997"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.1999.7346"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-17-06340.2000"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.3389\/fvets.2023.1235163"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1065057"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn1242"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2006.03.011"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-42420-6"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2018.07.001"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.01.032"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200410136"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1042\/NS20160007"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00770-0"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.05.033"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.07.001"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1177\/1073858417712668"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2016.03.004"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI82409"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-17-06597.2001"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2017.00572"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.WCB.0000035040.10031.B0"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4128-11.2012"},{"key":"e_1_3_2_49_2","first-page":"261","article-title":"Fabrication of a microfluidic device for the compartmentalization of neuron soma and axons","volume":"7","author":"Harris J.","year":"2007","unstructured":"J. Harris, H. Lee, B. Vahidi, C. Tu, D. Cribbs, N. L. Jeon, C. Cotman, Fabrication of a microfluidic device for the compartmentalization of neuron soma and axons. J. Vis. Exp. 7, 261 (2007).","journal-title":"J. Vis. Exp."},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth777"},{"key":"e_1_3_2_51_2","first-page":"51795","article-title":"Production and isolation of axons from sensory neurons for biochemical analysis using porous filters","volume":"89","author":"Unsain N.","year":"2014","unstructured":"N. Unsain, K. N. Heard, J. M. Higgins, P. A. Barker, Production and isolation of axons from sensory neurons for biochemical analysis using porous filters. J. Vis. Exp. 89, 51795 (2014).","journal-title":"J. Vis. Exp."},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1314"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3643-04.2004"}],"container-title":["Science Signaling"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/scisignal.adn2616","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,24]],"date-time":"2024-09-24T17:58:20Z","timestamp":1727200700000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/scisignal.adn2616"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,24]]},"references-count":52,"journal-issue":{"issue":"855","published-print":{"date-parts":[[2024,9,24]]}},"alternative-id":["10.1126\/scisignal.adn2616"],"URL":"https:\/\/doi.org\/10.1126\/scisignal.adn2616","relation":{},"ISSN":["1945-0877","1937-9145"],"issn-type":[{"value":"1945-0877","type":"print"},{"value":"1937-9145","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,24]]},"assertion":[{"value":"2023-12-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-08-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-24","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eadn2616"}}