دورية أكاديمية
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NVP-BEZ235 (Dactolisib) Has Protective Effects in a Transgenic Mouse Model of Alzheimer's Disease.

التفاصيل البيبلوغرافية
العنوان: NVP-BEZ235 (Dactolisib) Has Protective Effects in a Transgenic Mouse Model of Alzheimer's Disease.
المؤلفون: Bellozi PMQ; Department of Pharmacology, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil., Gomes GF; Department of Pharmacology, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil., de Oliveira LR; Department of Pharmacology, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil., Olmo IG; Department of Biochemistry and Immunology, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil., Vieira ÉLM; Department of Internal Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil., Ribeiro FM; Department of Biochemistry and Immunology, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil., Fiebich BL; Neuroimmunology and Neurochemistry Research Group, Department of Psychiatry and Psychotherapy, Medical Center-University of Freiburg, Faculty of Medicine, Freiburg im Breisgau, Germany., de Oliveira ACP; Department of Pharmacology, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
المصدر: Frontiers in pharmacology [Front Pharmacol] 2019 Nov 13; Vol. 10, pp. 1345. Date of Electronic Publication: 2019 Nov 13 (Print Publication: 2019).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Frontiers Media] Country of Publication: Switzerland NLM ID: 101548923 Publication Model: eCollection Cited Medium: Print ISSN: 1663-9812 (Print) Linking ISSN: 16639812 NLM ISO Abbreviation: Front Pharmacol Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: [Lausanne : Frontiers Media]
مستخلص: Alzheimer's disease (AD) is a neurodegenerative disease and the main cause of dementia. Its major symptom is memory loss, which is a result of neuronal cell death, which is accompanied by neuroinflammation. Some studies indicate the overactivation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mechanistic target of rapamycin (mTOR) pathway in this disease, being, thus, a potential target for pharmacological treatment. Here, we used a transgenic mouse model of AD that expresses a mutant amyloid-β precursor protein (T41 mice) to investigate the effects of dactolisib (alternative name: NVP-BEZ235, abbreviation BEZ), a dual PI3K/mTOR inhibitor. Ten-months-old T41 animals were treated for 14 days with BEZ or vehicle via oral gavage and then submitted to social memory, open field and contextual conditioned fear tests. Hippocampal slices were prepared and Aβ 1-42 content, NeuN, Iba-1, CD68 and GFAP were evaluated. Tissues were further processed to evaluate cytokines levels through cytometric bead array. The treatment with BEZ (5 mg/kg) reduced social memory impairment in T41 mice. However, BEZ did not have any effect on altered Aβ levels, NeuN, or GFAP staining. The drug reduced the CD68/Iba-1 ratio in CA3 region of hippocampus. Finally, BEZ diminished IL-10 levels in T41 mice. Thus, although its mechanisms are not clear, BEZ protects against memory impairment, reduces microglial activation and reestablishes IL-10 levels, revealing beneficial effects, which should be further investigated for the treatment of AD.
(Copyright © 2019 Bellozi, Gomes, de Oliveira, Olmo, Vieira, Ribeiro, Fiebich and de Oliveira.)
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فهرسة مساهمة: Keywords: Alzheimer’s disease; NVP-BEZ235; PI3K; dactolisib; mechanistic target of rapamycin; neurodegeneration; neuroinflammation
تواريخ الأحداث: Date Created: 20191205 Latest Revision: 20201001
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC6864823
DOI: 10.3389/fphar.2019.01345
PMID: 31798451
قاعدة البيانات: MEDLINE
الوصف
تدمد:1663-9812
DOI:10.3389/fphar.2019.01345