{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T08:02:00Z","timestamp":1780387320166,"version":"3.54.1"},"reference-count":111,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2019,10,14]],"date-time":"2019-10-14T00:00:00Z","timestamp":1571011200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2019,11,26]]},"abstract":"<jats:p>\n                    Cerebral hypoperfusion-induced hypoxia, a condition that impairs oxygen utilization and thus ATP production by mitochondrial oxidative phosphorylation (oxphos), is thought to contribute to neural degeneration in Alzheimer\u2019s disease. However, hypoxia upregulates the generation of amyloid-\u03b2 (A\u03b2), a group of peptides known to impair\/inhibit the electron transport chain (ETC) of reactions that support oxphos in the inner mitochondrial membrane (IMM). This is a hypothesis paper that reconciles the hypoxia-induced upregulation of A\u03b2 with A\u03b2\u2019s ETC-inhibiting action and, specifically, posits an oxphos-enhancing effect of this inhibition under conditions of newly developing or otherwise mild hypoxia. This effect is typically transient; that is, under conditions of prolonged or severe hypoxia, the oxphos-enhancing activity is overwhelmed by A\u03b2\u2019s well-known toxic actions on mitochondria and other cellular components. The hypothesis is motivated by evidence that the IMM transmembrane potential \u03a8\n                    <jats:sub>m<\/jats:sub>\n                    , an important determinant of ETC activity, exhibits heterogeneity, i.e., a range of values, among a given local population of mitochondria. It specifically proposes that during oxygen limitation, A\u03b2 selectively inactivates ETC complexes in mitochondria that exhibit relatively low absolute values of \u03a8\n                    <jats:sub>m<\/jats:sub>\n                    , thereby suppressing oxygen binding and consumption by complex IV of the ETC in these mitochondria. This effect of A\u03b2 on low- \u03a8\n                    <jats:sub>m<\/jats:sub>\n                    mitochondria is hypothesized to spare hypoxia-limited oxygen for oxphos-enabling utilization by the ETC of the remaining active, higher- \u03a8\n                    <jats:sub>m<\/jats:sub>\n                    local mitochondria, and thereby to increase overall ATP generated collectively by the local mitochondrial population, i.e., to ameliorate hypoxia-induced oxphos reduction. The protective action of A\u03b2 hypothesized here may slow the early development of hypoxia-associated cellular deterioration\/loss in Alzheimer\u2019s disease and perhaps other neurodegenerative diseases.\n                  <\/jats:p>","DOI":"10.3233\/jad-190476","type":"journal-article","created":{"date-parts":[[2019,10,15]],"date-time":"2019-10-15T18:01:09Z","timestamp":1571162469000},"page":"663-675","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":6,"title":["Amyloid-\u03b2-Dependent Inactivation of the Mitochondrial Electron Transport Chain at Low Transmembrane Potential: An Ameliorating Process in Hypoxia-Associated Neurodegenerative Disease?"],"prefix":"10.1177","volume":"72","author":[{"given":"David R.","family":"Pepperberg","sequence":"first","affiliation":[{"name":"Lions of Illinois Eye Research Institute, Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, University of Illinois at Chicago, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2019,10,14]]},"reference":[{"key":"ref001","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-385883-2.00012-6"},{"key":"ref002","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3028"},{"key":"ref003","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4018"},{"key":"ref004","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-179941"},{"key":"ref005","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2013.10.008"},{"key":"ref006","doi-asserted-by":"publisher","DOI":"10.5853\/jos.2015.17.1.17"},{"key":"ref007","doi-asserted-by":"publisher","DOI":"10.1038\/nrn.2017.29"},{"key":"ref008","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2017.03.003"},{"key":"ref009","doi-asserted-by":"publisher","DOI":"10.4061\/2011\/198430"},{"key":"ref010","doi-asserted-by":"publisher","DOI":"10.2174\/1567205010666131119235254"},{"key":"ref011","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-014-8740-7"},{"key":"ref012","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.12.056"},{"key":"ref013","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2017.111"},{"key":"ref014","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2009-17.2017"},{"key":"ref015","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.11.009"},{"key":"ref016","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-170490"},{"key":"ref017","doi-asserted-by":"publisher","DOI":"10.1126\/science.1091230"},{"key":"ref018","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1868"},{"key":"ref019","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4717-10.2011"},{"key":"ref020","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-394625-6.00007-6"},{"key":"ref021","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-015-9515-5"},{"key":"ref022","doi-asserted-by":"publisher","DOI":"10.1042\/BST20170024"},{"key":"ref023","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-170585"},{"key":"ref024","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2001.00112.x"},{"key":"ref025","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2006.04050.x"},{"key":"ref026","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0905529106"},{"key":"ref027","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0042344"},{"key":"ref028","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2013.03.008"},{"key":"ref029","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-10233-0"},{"key":"ref030","doi-asserted-by":"publisher","DOI":"10.1038\/191144a0"},{"key":"ref031","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(99)01534-9"},{"key":"ref032","first-page":"37","volume-title":"Navigating Metabolism","author":"Chandel NS","year":"2015"},{"key":"ref033","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-140144"},{"key":"ref034","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2015.12.016"},{"key":"ref035","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-161266"},{"key":"ref036","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-017-0570-2"},{"key":"ref037","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-180004"},{"key":"ref038","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.9.4304"},{"key":"ref039","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0449-07.2007"},{"key":"ref040","doi-asserted-by":"publisher","DOI":"10.1111\/1440-1681.12717"},{"key":"ref041","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0606298103"},{"key":"ref042","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M608856200"},{"key":"ref043","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2008.05858.x"},{"key":"ref044","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.13932"},{"key":"ref045","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0170345"},{"key":"ref046","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00050.2017"},{"key":"ref047","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2013.09.003"},{"key":"ref048","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11483"},{"key":"ref049","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0168840"},{"key":"ref050","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5170-04.2005"},{"key":"ref051","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2008.96"},{"key":"ref052","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-13-05531.2003"},{"key":"ref053","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2433"},{"key":"ref054","first-page":"479","volume":"88","author":"Morley JE","year":"2014","journal-title":"Pharmacol"},{"key":"ref055","doi-asserted-by":"publisher","DOI":"10.1038\/srep32553"},{"key":"ref056","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3607-16.2017"},{"key":"ref057","doi-asserted-by":"publisher","DOI":"10.2174\/156720506775697124"},{"key":"ref058","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0042665"},{"key":"ref059","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaf1059"},{"key":"ref060","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2017.05.022"},{"key":"ref061","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0019191"},{"key":"ref062","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.25998"},{"key":"ref063","doi-asserted-by":"publisher","DOI":"10.1007\/s10522-017-9692-x"},{"key":"ref064","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.12964"},{"key":"ref065","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-170543"},{"key":"ref066","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbabio.2008.05.001"},{"key":"ref067","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2017.7203"},{"key":"ref068","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(01)00688-8"},{"key":"ref069","first-page":"113","volume":"2","author":"Chinwern Chan AD","year":"1999","journal-title":"Alzheimers Rep"},{"key":"ref070","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-12-04833.2002"},{"key":"ref071","doi-asserted-by":"publisher","DOI":"10.1016\/0891-5849(95)02207-4"},{"key":"ref072","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0974-04.2004"},{"key":"ref073","doi-asserted-by":"publisher","DOI":"10.1016\/0197-4580(92)90059-7"},{"key":"ref074","doi-asserted-by":"publisher","DOI":"10.1016\/0197-4580(92)90057-5"},{"key":"ref075","doi-asserted-by":"publisher","DOI":"10.3109\/13506129809007283"},{"key":"ref076","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2011.4173"},{"key":"ref077","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2012.09.036"},{"key":"ref078","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(02)01021-3"},{"key":"ref079","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1736-09.2009"},{"key":"ref080","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2009.06.130"},{"key":"ref081","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-199511270-00031"},{"key":"ref082","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(95)00539-W"},{"key":"ref083","first-page":"45","volume":"1","author":"Koudinov A","year":"2003","journal-title":"Neurobiol Lipids"},{"key":"ref084","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2692-08.2008"},{"key":"ref085","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22313"},{"key":"ref086","doi-asserted-by":"publisher","DOI":"10.1101\/lm.1310209"},{"key":"ref087","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2011.12.020"},{"key":"ref088","doi-asserted-by":"publisher","DOI":"10.1039\/C7CP05959K"},{"key":"ref089","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2017.02.043"},{"key":"ref090","doi-asserted-by":"publisher","DOI":"10.2337\/db06-0757"},{"key":"ref091","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2009.06.006"},{"key":"ref092","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.140093597"},{"key":"ref093","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2009.08.008"},{"key":"ref094","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2011.04.004"},{"key":"ref095","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1202753"},{"key":"ref096","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2013.12.003"},{"key":"ref097","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(12)70291-0"},{"key":"ref098","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(18)30028-0"},{"key":"ref099","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2255-14.2014"},{"key":"ref100","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.1500472"},{"key":"ref101","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1705235114"},{"key":"ref102","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-017-0020-4"},{"key":"ref103","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-130419"},{"key":"ref104","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-130728"},{"key":"ref105","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.117.311054"},{"key":"ref106","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0806192105"},{"key":"ref107","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-132543"},{"key":"ref108","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-160953"},{"key":"ref109","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2017.204"},{"key":"ref110","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.11.6448"},{"key":"ref111","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.264473"}],"container-title":["Journal of Alzheimer\u2019s Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/JAD-190476","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.3233\/JAD-190476","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/JAD-190476","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T10:07:00Z","timestamp":1777370820000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.3233\/JAD-190476"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,14]]},"references-count":111,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2019,11,26]]}},"alternative-id":["10.3233\/JAD-190476"],"URL":"https:\/\/doi.org\/10.3233\/jad-190476","relation":{},"ISSN":["1387-2877","1875-8908"],"issn-type":[{"value":"1387-2877","type":"print"},{"value":"1875-8908","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,14]]}}}