{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T22:21:28Z","timestamp":1791066088545,"version":"4.1.0"},"reference-count":50,"publisher":"National Academy of Sciences","issue":"14","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2010,4,6]]},"abstract":"<jats:p>\n                    Full-length amyloid beta peptides (A\u03b2\n                    <jats:sub>1\u201340\/42<\/jats:sub>\n                    ) form neuritic amyloid plaques in Alzheimer\u2019s disease (AD) patients and are implicated in AD pathology. However, recent transgenic animal models cast doubt on their direct role in AD pathology. Nonamyloidogenic truncated amyloid-beta fragments (A\u03b2\n                    <jats:sub>11\u201342<\/jats:sub>\n                    and A\u03b2\n                    <jats:sub>17\u201342<\/jats:sub>\n                    ) are also found in amyloid plaques of AD and in the preamyloid lesions of Down syndrome, a model system for early-onset AD study. Very little is known about the structure and activity of these smaller peptides, although they could be the primary AD and Down syndrome pathological agents. Using complementary techniques of molecular dynamics simulations, atomic force microscopy, channel conductance measurements, calcium imaging, neuritic degeneration, and cell death assays, we show that nonamyloidogenic A\u03b2\n                    <jats:sub>9\u201342<\/jats:sub>\n                    and A\u03b2\n                    <jats:sub>17\u201342<\/jats:sub>\n                    peptides form ion channels with loosely attached subunits and elicit single-channel conductances. The subunits appear mobile, suggesting insertion of small oligomers, followed by dynamic channel assembly and dissociation. These channels allow calcium uptake in amyloid precursor protein-deficient cells. The channel mediated calcium uptake induces neurite degeneration in human cortical neurons. Channel conductance, calcium uptake, and neurite degeneration are selectively inhibited by zinc, a blocker of amyloid ion channel activity. Thus, truncated A\u03b2 fragments could account for undefined roles played by full length A\u03b2s and provide a unique mechanism of AD and Down syndrome pathologies. The toxicity of nonamyloidogenic peptides via an ion channel mechanism necessitates a reevaluation of the current therapeutic approaches targeting the nonamyloidogenic pathway as avenue for AD treatment.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0914251107","type":"journal-article","created":{"date-parts":[[2010,3,22]],"date-time":"2010-03-22T22:36:27Z","timestamp":1269297387000},"page":"6538-6543","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":210,"title":["Truncated \u03b2-amyloid peptide channels provide an alternative mechanism for Alzheimer\u2019s Disease and Down syndrome"],"prefix":"10.1073","volume":"107","author":[{"given":"Hyunbum","family":"Jang","sequence":"first","affiliation":[{"name":"Center for Cancer Research Nanobiology Program, SAIC-Frederick, Inc., National Cancer Institute, Frederick, MD 21702;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando Teran","family":"Arce","sequence":"additional","affiliation":[{"name":"Center for Nanomedicine and Department of Medicine, University of Chicago, Chicago, IL 60637;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srinivasan","family":"Ramachandran","sequence":"additional","affiliation":[{"name":"Center for Nanomedicine and Department of Medicine, University of Chicago, Chicago, IL 60637;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Capone","sequence":"additional","affiliation":[{"name":"Center for Nanomedicine and Department of Medicine, University of Chicago, Chicago, IL 60637;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rushana","family":"Azimova","sequence":"additional","affiliation":[{"name":"Semel Neuropsychiatric Institute, The David Geffen School of Medicine, University of California at Los Angeles and Greater Los Angeles Veterans Administration Health System, Los Angeles, CA 90024; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce L.","family":"Kagan","sequence":"additional","affiliation":[{"name":"Semel Neuropsychiatric Institute, The David Geffen School of Medicine, University of California at Los Angeles and Greater Los Angeles Veterans Administration Health System, Los Angeles, CA 90024; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Nussinov","sequence":"additional","affiliation":[{"name":"Center for Cancer Research Nanobiology Program, SAIC-Frederick, Inc., National Cancer Institute, Frederick, MD 21702;"},{"name":"Department of Human Molecular Genetics and Biochemistry, The Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ratnesh","family":"Lal","sequence":"additional","affiliation":[{"name":"Center for Nanomedicine and Department of Medicine, University of Chicago, Chicago, IL 60637;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2010,3,22]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1038\/416507a","article-title":"Inherent toxicity of aggregates implies a common mechanism for protein misfolding diseases","volume":"416","author":"Bucciantini M","year":"2002","unstructured":"M Bucciantini, et al., Inherent toxicity of aggregates implies a common mechanism for protein misfolding diseases. Nature 416, 507\u2013511 (2002).","journal-title":"Nature"},{"key":"e_1_3_4_2_2","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1038\/416535a","article-title":"Naturally secreted oligomers of amyloid \u03b2 protein potently inhibit hippocampal long-term potentiation in vivo","volume":"416","author":"Walsh DM","year":"2002","unstructured":"DM Walsh, et al., Naturally secreted oligomers of amyloid \u03b2 protein potently inhibit hippocampal long-term potentiation in vivo. 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(2005).","journal-title":"Science"},{"key":"e_1_3_4_5_2","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.tibs.2007.10.007","article-title":"New structures help the modeling of toxic amyloidbeta ion channels","volume":"33","author":"Jang H","year":"2008","unstructured":"H Jang, J Zheng, R Lal, R Nussinov, New structures help the modeling of toxic amyloidbeta ion channels. Trends Biochem Sci 33, 91\u2013100 (2008).","journal-title":"Trends Biochem Sci"},{"key":"e_1_3_4_6_2","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1038\/418291a","article-title":"Neurodegenerative disease: amyloid pores from pathogenic mutations","volume":"418","author":"Lashuel HA","year":"2002","unstructured":"HA Lashuel, D Hartley, BM Petre, T Walz, PT Lansbury, Neurodegenerative disease: amyloid pores from pathogenic mutations. 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J Biol Chem 275, 14077\u201314083 (2000).","journal-title":"J Biol Chem"},{"key":"e_1_3_4_13_2","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1002\/(SICI)1097-4547(19990815)57:4<458::AID-JNR5>3.0.CO;2-4","article-title":"Alzheimer amyloid abeta1-42 channels: effects of solvent, pH, and Congo Red","volume":"57","author":"Hirakura Y","year":"1999","unstructured":"Y Hirakura, MC Lin, BL Kagan, Alzheimer amyloid abeta1-42 channels: effects of solvent, pH, and Congo Red. J Neurosci Res 57, 458\u2013466 (1999).","journal-title":"J Neurosci Res"},{"key":"e_1_3_4_14_2","doi-asserted-by":"crossref","first-page":"194","DOI":"10.3109\/13506120009146834","article-title":"Amyloid peptide channels: blockade by zinc and inhibition by Congo red (amyloid channel block)","volume":"7","author":"Hirakura Y","year":"2000","unstructured":"Y Hirakura, WW Yiu, A Yamamoto, BL Kagan, Amyloid peptide channels: blockade by zinc and inhibition by Congo red (amyloid channel block). 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Biochem J 313, 575\u2013580 (1996).","journal-title":"Biochem J"},{"key":"e_1_3_4_21_2","doi-asserted-by":"crossref","first-page":"33623","DOI":"10.1074\/jbc.271.52.33623","article-title":"The \u201cnonamyloidogenic\u201d p3 fragment (amyloid \u03b217-42) is a major constituent of Down\u2019s syndrome cerebellar preamyloid","volume":"271","author":"Lalowski M","year":"1996","unstructured":"M Lalowski, et al., The \u201cnonamyloidogenic\u201d p3 fragment (amyloid \u03b217-42) is a major constituent of Down\u2019s syndrome cerebellar preamyloid. 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J Biol Chem 270, 23895\u201323898 (1995).","journal-title":"J Biol Chem"},{"key":"e_1_3_4_25_2","doi-asserted-by":"crossref","first-page":"1938","DOI":"10.1529\/biophysj.107.110148","article-title":"Models of \u03b2-amyloid ion channels in the membrane suggest that channel formation in the bilayer is a dynamic process","volume":"93","author":"Jang H","year":"2007","unstructured":"H Jang, J Zheng, R Nussinov, Models of \u03b2-amyloid ion channels in the membrane suggest that channel formation in the bilayer is a dynamic process. 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Proc Natl Acad Sci USA 102, 17342\u201317347 (2005).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_28_2","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1021\/bi051952q","article-title":"Experimental constraints on quaternary structure in Alzheimer\u2019s \u03b2-amyloid fibrils","volume":"45","author":"Petkova AT","year":"2006","unstructured":"AT Petkova, WM Yau, R Tycko, Experimental constraints on quaternary structure in Alzheimer\u2019s \u03b2-amyloid fibrils. Biochemistry 45, 498\u2013512 (2006).","journal-title":"Biochemistry"},{"key":"e_1_3_4_29_2","doi-asserted-by":"crossref","first-page":"18119","DOI":"10.1073\/pnas.0607180103","article-title":"3D structure of amyloid protofilaments of \u03b22-microglobulin fragment probed by solid-state NMR","volume":"103","author":"Iwata K","year":"2006","unstructured":"K Iwata, et al., 3D structure of amyloid protofilaments of \u03b22-microglobulin fragment probed by solid-state NMR. Proc Natl Acad Sci USA 103, 18119\u201318124 (2006).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_30_2","doi-asserted-by":"crossref","first-page":"16248","DOI":"10.1073\/pnas.0607815103","article-title":"General structural motifs of amyloid protofilaments","volume":"103","author":"Ferguson N","year":"2006","unstructured":"N Ferguson, et al., General structural motifs of amyloid protofilaments. Proc Natl Acad Sci USA 103, 16248\u201316253 (2006).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_31_2","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1074\/jbc.272.1.44","article-title":"Channel formation by a neurotoxic prion protein fragment","volume":"272","author":"Lin MC","year":"1997","unstructured":"MC Lin, T Mirzabekov, BL Kagan, Channel formation by a neurotoxic prion protein fragment. J Biol Chem 272, 44\u201347 (1997).","journal-title":"J Biol Chem"},{"key":"e_1_3_4_32_2","doi-asserted-by":"crossref","first-page":"94","DOI":"10.3109\/13506120109007350","article-title":"Pore formation by \u03b2-2-microglobulin: a mechanism for the pathogenesis of dialysis associated amyloidosis","volume":"8","author":"Hirakura Y","year":"2001","unstructured":"Y Hirakura, BL Kagan, Pore formation by \u03b2-2-microglobulin: a mechanism for the pathogenesis of dialysis associated amyloidosis. Amyloid 8, 94\u2013100 (2001).","journal-title":"Amyloid"},{"key":"e_1_3_4_33_2","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1126\/science.318.5849.384","article-title":"Alzheimer\u2019s disease. Fresh evidence points to an old suspect: calcium","volume":"318","author":"Marx J","year":"2007","unstructured":"J Marx, Alzheimer\u2019s disease. Fresh evidence points to an old suspect: calcium. Science 318, 384\u2013385 (2007).","journal-title":"Science"},{"key":"e_1_3_4_34_2","doi-asserted-by":"crossref","first-page":"14938","DOI":"10.1021\/ja9049299","article-title":"K3 fragment of amyloidogenic beta(2)-microglobulin forms ion channels: implication for dialysis related amyloidosis","volume":"131","author":"Mustata M","year":"2009","unstructured":"M Mustata, et al., K3 fragment of amyloidogenic beta(2)-microglobulin forms ion channels: implication for dialysis related amyloidosis. J Am Chem Soc 131, 14938\u201314945 (2009).","journal-title":"J Am Chem Soc"},{"key":"e_1_3_4_35_2","doi-asserted-by":"crossref","first-page":"4631","DOI":"10.1529\/biophysj.108.134551","article-title":"Models of toxic \u03b2-sheet channels of protegrin-1 suggest a common subunit organization motif shared with toxic alzheimer \u03b2-amyloid ion channels","volume":"95","author":"Jang H","year":"2008","unstructured":"H Jang, B Ma, R Lal, R Nussinov, Models of toxic \u03b2-sheet channels of protegrin-1 suggest a common subunit organization motif shared with toxic alzheimer \u03b2-amyloid ion channels. Biophys J 95, 4631\u20134642 (2008).","journal-title":"Biophys J"},{"key":"e_1_3_4_36_2","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1016\/j.febslet.2008.05.002","article-title":"P3 peptide, a truncated form of A \u03b2 devoid of synaptotoxic effect, does not assemble into soluble oligomers","volume":"582","author":"Dulin F","year":"2008","unstructured":"F Dulin, et al., P3 peptide, a truncated form of A \u03b2 devoid of synaptotoxic effect, does not assemble into soluble oligomers. FEBS Lett 582, 1865\u20131870 (2008).","journal-title":"FEBS Lett"},{"key":"e_1_3_4_37_2","doi-asserted-by":"crossref","first-page":"1456","DOI":"10.1172\/JCI20864","article-title":"A disintegrin-metalloproteinase prevents amyloid plaque formation and hippocampal defects in an Alzheimer disease mouse model","volume":"113","author":"Postina R","year":"2004","unstructured":"R Postina, et al., A disintegrin-metalloproteinase prevents amyloid plaque formation and hippocampal defects in an Alzheimer disease mouse model. J Clin Invest 113, 1456\u20131464 (2004).","journal-title":"J Clin Invest"},{"key":"e_1_3_4_38_2","doi-asserted-by":"crossref","first-page":"2117","DOI":"10.1523\/JNEUROSCI.14-04-02117.1994","article-title":"A heparin-binding domain in the amyloid protein precursor of Alzheimer\u2019s disease is involved in the regulation of neurite outgrowth","volume":"14","author":"Small DH","year":"1994","unstructured":"DH Small, et al., A heparin-binding domain in the amyloid protein precursor of Alzheimer\u2019s disease is involved in the regulation of neurite outgrowth. J Neurosci 14, 2117\u20132127 (1994).","journal-title":"J Neurosci"},{"key":"e_1_3_4_39_2","doi-asserted-by":"crossref","first-page":"1882","DOI":"10.1046\/j.1471-4159.1996.67051882.x","article-title":"Increased activity-regulating and neuroprotective efficacy of alpha-secretase-derived secreted amyloid precursor protein conferred by a C-terminal heparin-binding domain","volume":"67","author":"Furukawa K","year":"1996","unstructured":"K Furukawa, et al., Increased activity-regulating and neuroprotective efficacy of alpha-secretase-derived secreted amyloid precursor protein conferred by a C-terminal heparin-binding domain. J Neurochem 67, 1882\u20131896 (1996).","journal-title":"J Neurochem"},{"key":"e_1_3_4_40_2","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.bbrc.2005.03.074","article-title":"Alzheimer\u2019s disease: channeling APP to non-amyloidogenic processing","volume":"331","author":"Tang BL","year":"2005","unstructured":"BL Tang, Alzheimer\u2019s disease: channeling APP to non-amyloidogenic processing. Biochem Biophys Res Commun 331, 375\u2013378 (2005).","journal-title":"Biochem Biophys Res Commun"},{"key":"e_1_3_4_41_2","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.mam.2008.08.001","article-title":"The ADAM metalloproteinases","volume":"29","author":"Edwards DR","year":"2008","unstructured":"DR Edwards, MM Handsley, CJ Pennington, The ADAM metalloproteinases. 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