{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T12:00:04Z","timestamp":1791979204556,"version":"4.4.0"},"reference-count":50,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2020,5,21]],"date-time":"2020-05-21T00:00:00Z","timestamp":1590019200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013129","name":"Ministry of SMEs and Startups","doi-asserted-by":"publisher","award":["S2566811"],"award-info":[{"award-number":["S2566811"]}],"id":[{"id":"10.13039\/501100013129","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is a complex, age-related neurodegenerative disease that is the most common form of dementia. However, the cure for AD has not yet been founded. The accumulation of amyloid beta (A\u03b2) is considered to be a hallmark of AD. Beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), also known as beta secretase is the initiating enzyme in the amyloidogenic pathway. Blocking BACE1 could reduce the amount of A\u03b2, but this would also prohibit the other functions of BACE1 in brain physiological activity. SPONDIN1 (SPON1) is known to bind to the BACE1 binding site of the amyloid precursor protein (APP) and blocks the initiating amyloidogenesis. Here, we show the effect of SPON1 in A\u03b2 reduction in vitro in neural cells and in an in vivo AD mouse model. We engineered mouse induced neural stem cells (iNSCs) to express Spon1. iNSCs harboring mouse Spon1 secreted SPON1 protein and reduced the quantity of A\u03b2 when co-cultured with A\u03b2-secreting Neuro 2a cells. The human SPON1 gene itself also reduced A\u03b2 in HEK 293T cells expressing the human APP transgene with AD-linked mutations through lentiviral-mediated delivery. We also demonstrated that injecting SPON1 reduced the amount of A\u03b2 and ameliorated cognitive dysfunction and memory impairment in 5xFAD mice expressing human APP and PSEN1 transgenes with five AD-linked mutations.<\/jats:p>","DOI":"10.3390\/cells9051275","type":"journal-article","created":{"date-parts":[[2020,5,21]],"date-time":"2020-05-21T11:31:18Z","timestamp":1590060678000},"page":"1275","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["SPON1 Can Reduce Amyloid Beta and Reverse Cognitive Impairment and Memory Dysfunction in Alzheimer\u2019s Disease Mouse Model"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0709-2388","authenticated-orcid":false,"given":"Soo Yong","family":"Park","sequence":"first","affiliation":[{"name":"Stem Cell Research Center, School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joo Yeong","family":"Kang","sequence":"additional","affiliation":[{"name":"Stem Cell Research Center, School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taehee","family":"Lee","sequence":"additional","affiliation":[{"name":"Stem Cell Research Center, School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donggyu","family":"Nam","sequence":"additional","affiliation":[{"name":"Stem Cell Research Center, School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0492-6735","authenticated-orcid":false,"given":"Chang-Jin","family":"Jeon","sequence":"additional","affiliation":[{"name":"Neuroscience Laboratory, Department of Biology, College of Natural Sciences, Kyungpook National University, Daegu 41566, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6230-8826","authenticated-orcid":false,"given":"Jeong Beom","family":"Kim","sequence":"additional","affiliation":[{"name":"Stem Cell Research Center, School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1212\/WNL.42.1.115","article-title":"Prevalence of dementia and probable senile dementia of the Alzheimer type in the Framingham Study","volume":"42","author":"Bachman","year":"1992","journal-title":"Neurology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/S0140-6736(15)01124-1","article-title":"Alzheimer\u2019s disease","volume":"388","author":"Scheltens","year":"2016","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1080\/13543784.2017.1323868","article-title":"Why do trials for Alzheimer\u2019s disease drugs keep failing? 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