{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T16:41:55Z","timestamp":1777394515837,"version":"3.51.4"},"reference-count":0,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2013,12,10]],"date-time":"2013-12-10T00:00:00Z","timestamp":1386633600000},"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":[[2013,12,10]]},"abstract":"<jats:p>\u03b2-Secretase-1 (BACE1) is the rate-limiting enzyme for the genesis of amyloid-\u03b2 (A\u03b2) peptides, the main constituents of the amyloid plaques in the brains of Alzheimer's disease (AD) patients. BACE1 is being evaluated as an anti-A\u03b2 target for AD therapy. Recent studies indicate that BACE1 elevation is associated with axonal and presynaptic pathology during plaque development. Evidence also points to a biological role for BACE1 in axonal outgrowth and synapse formation during development. Axonal, including presynaptic, pathology exists in AD as well as many other neurological disorders such as Parkinson's disease, epilepsy, stroke, and trauma. In this review, we discuss pharmaceutical BACE1 inhibition as a therapeutic option for axonal pathogenesis, in addition to amyloid pathology. We first introduce the amyloidogenic processing of amyloid-\u03b2 protein precursor and describe the normal expression pattern of the amyloidogenic proteins in the brain, with an emphasis on BACE1. We then address BACE1 elevation relative to amyloid plaque development, followed by updating recent understanding of a neurotrophic role of BACE1 in axon and synapse development. We further elaborate the occurrence of axonal pathology in some other neurological conditions. Finally, we propose pharmacological inhibition of excessive BACE1 activity as an option to mitigate early axonal pathology occurring in AD and other neurological disorders.<\/jats:p>","DOI":"10.3233\/jad-131400","type":"journal-article","created":{"date-parts":[[2018,6,4]],"date-time":"2018-06-04T12:15:39Z","timestamp":1528114539000},"page":"705-718","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":19,"title":["Can BACE1 Inhibition Mitigate Early Axonal Pathology in Neurological Diseases?"],"prefix":"10.1177","volume":"38","author":[{"given":"Xiao-Xin","family":"Yan","sequence":"first","affiliation":[{"name":"Department of Anatomy and Neurobiology, Central South University Xiangya School of Medicine, Changsha, Hunan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Histology and Embryology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences &amp; Peking Union Medical College, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei-Ping","family":"Gai","sequence":"additional","affiliation":[{"name":"Department of Human Physiology and Centre for Neuroscience, Flinders University School of Medicine, Bedford Park, SA, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huaibin","family":"Cai","sequence":"additional","affiliation":[{"name":"Transgenics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xue-Gang","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurobiology, Central South University Xiangya School of Medicine, Changsha, Hunan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2013,12,10]]},"container-title":["Journal of Alzheimer\u2019s Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/JAD-131400","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/JAD-131400","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T10:03:32Z","timestamp":1777370612000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.3233\/JAD-131400"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,12,10]]},"references-count":0,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2013,12,10]]}},"alternative-id":["10.3233\/JAD-131400"],"URL":"https:\/\/doi.org\/10.3233\/jad-131400","relation":{},"ISSN":["1387-2877","1875-8908"],"issn-type":[{"value":"1387-2877","type":"print"},{"value":"1875-8908","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,12,10]]}}}