{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T16:59:27Z","timestamp":1777395567088,"version":"3.51.4"},"reference-count":89,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2021,7,21]],"date-time":"2021-07-21T00:00:00Z","timestamp":1626825600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2021,7,21]]},"abstract":"<jats:p>Background: Alzheimer\u2019s disease (AD) is a progressive neurodegenerative disorder characterized by impairments in synaptic plasticity and cognitive performance. Cognitive dysfunction and loss of neuronal plasticity are known to begin decades before the clinical diagnosis of the disease. The important influence of congenital genetic mutations on the early development of AD provides a novel opportunity to initiate treatment during early development to prevent the Alzheimer-like behavior and synaptic dysfunction. Objective: To explore strategies for early intervention to prevent Alzheimer\u2019s disease. Methods: In the present study, we investigated the effect of treatment during early development with a ciliary neurotrophic factor (CNTF) derived peptidergic compound, P021 (Ac-DGGLAG-NH2) on cognitive function and synaptic plasticity in 3xTg-AD transgenic mouse model of AD. 3xTg-AD and genetic background-matched wild type female mice were treated from birth to postnatal day 120 with P021 in diet or as a control with vehicle diet, and cognitive function and molecular markers of neuroplasticity were evaluated. Results: P021 treatment during early development prevented cognitive impairment and increased expressions of pCREB and BDNF that activated downstream various signaling cascades such as PLC\/PKC, MEK\/ERK and PI3K\/Akt, and ameliorated synaptic protein deficit in 4-month-old 3xTg-AD mice. Conclusion: These findings indicate that treatment with the neurotrophic peptide mimetic such as P021 during early development can be an effective therapeutic strategy to rescue synaptic deficit and cognitive impairment in familial AD and related tauopathies.<\/jats:p>","DOI":"10.3233\/jad-201599","type":"journal-article","created":{"date-parts":[[2021,5,28]],"date-time":"2021-05-28T15:25:03Z","timestamp":1622215503000},"page":"631-646","source":"Crossref","is-referenced-by-count":17,"title":["Neurotrophic Treatment Initiated During Early Postnatal Development Prevents the Alzheimer-Like Behavior and Synaptic Dysfunction"],"prefix":"10.1177","volume":"82","author":[{"given":"Wei","family":"Wei","sequence":"first","affiliation":[{"name":"Department of Neurochemistry, Inge Grundke-Iqbal Research Floor, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA"},{"name":"Key Laboratory of State Administration of Traditional Chinese Medicine of China, Department of Pathophysiology, School of Medicine, Institute of Brain Research, Jinan University, Guangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yinghua","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurochemistry, Inge Grundke-Iqbal Research Floor, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA"},{"name":"Department of Pharmacology, School of Pharmaceutical Sciences, Guangzhou Medical University, Key Laboratory of Molecular Clinical Pharmacology & Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chun-Ling","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Neurochemistry, Inge Grundke-Iqbal Research Floor, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Narjes","family":"Baazaoui","sequence":"additional","affiliation":[{"name":"Department of Neurochemistry, Inge Grundke-Iqbal Research Floor, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA"},{"name":"King Khalid University, Abha 61421, Abha, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunn Chyn","family":"Tung","sequence":"additional","affiliation":[{"name":"Department of Neurochemistry, Inge Grundke-Iqbal Research Floor, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurochemistry, Inge Grundke-Iqbal Research Floor, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khalid","family":"Iqbal","sequence":"additional","affiliation":[{"name":"Department of Neurochemistry, Inge Grundke-Iqbal Research Floor, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","reference":[{"key":"10.3233\/JAD-201599_ref1","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1007\/s00401-011-0878-z","article-title":"Opportunities and challenges in developing Alzheimer disease therapeutics","volume":"122","author":"Iqbal","year":"2011","journal-title":"Acta Neuropathol"},{"key":"10.3233\/JAD-201599_ref2","doi-asserted-by":"crossref","unstructured":"(2020) 2020 Alzheimer\u2019s disease facts and figures. 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