Neuroprotective Profile of Triazole Grandisin Analogue against Amyloid-Beta Oligomer-Induced Cognitive Impairment.

التفاصيل البيبلوغرافية
العنوان:	Neuroprotective Profile of Triazole Grandisin Analogue against Amyloid-Beta Oligomer-Induced Cognitive Impairment.
المؤلفون:	Andrade VHB; Pharmaceutical Sciences, Food and Nutrition School, Federal University of Mato Grosso do Sul (UFMS), Campo Grande 79051-470, Brazil., M Rodrigues EY; Pharmaceutical Sciences, Food and Nutrition School, Federal University of Mato Grosso do Sul (UFMS), Campo Grande 79051-470, Brazil., Dias NAF; School of Medicine, Federal University of Mato Grosso do Sul (UFMS), Campo Grande 79051-470, Brazil., Ferreira GFC; School of Medicine, Federal University of Mato Grosso do Sul (UFMS), Campo Grande 79051-470, Brazil., Carvalho DB; Pharmaceutical Sciences, Food and Nutrition School, Federal University of Mato Grosso do Sul (UFMS), Campo Grande 79051-470, Brazil., das Neves AR; Pharmaceutical Sciences, Food and Nutrition School, Federal University of Mato Grosso do Sul (UFMS), Campo Grande 79051-470, Brazil., Coronel PMV; Pharmaceutical Sciences, Food and Nutrition School, Federal University of Mato Grosso do Sul (UFMS), Campo Grande 79051-470, Brazil., Yonekawa MKA; Institute of Biosciences, Federal University of Mato Grosso do Sul (INBIO-UFMS), Campo Grande 79051-470, Brazil., Parisotto EB; Pharmaceutical Sciences, Food and Nutrition School, Federal University of Mato Grosso do Sul (UFMS), Campo Grande 79051-470, Brazil., Santos EAD; Institute of Biosciences, Federal University of Mato Grosso do Sul (INBIO-UFMS), Campo Grande 79051-470, Brazil., Souza AS; Institute of Biosciences, Federal University of Mato Grosso do Sul (INBIO-UFMS), Campo Grande 79051-470, Brazil., Paredes-Gamero EJ; Pharmaceutical Sciences, Food and Nutrition School, Federal University of Mato Grosso do Sul (UFMS), Campo Grande 79051-470, Brazil., de Sousa KS; Pharmaceutical Sciences, Food and Nutrition School, Federal University of Mato Grosso do Sul (UFMS), Campo Grande 79051-470, Brazil., Souza LL; Pharmaceutical Sciences, Food and Nutrition School, Federal University of Mato Grosso do Sul (UFMS), Campo Grande 79051-470, Brazil., Resstel LBM; School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14049-900, Brazil., Baroni ACM; Pharmaceutical Sciences, Food and Nutrition School, Federal University of Mato Grosso do Sul (UFMS), Campo Grande 79051-470, Brazil., Lagatta DC; Pharmaceutical Sciences, Food and Nutrition School, Federal University of Mato Grosso do Sul (UFMS), Campo Grande 79051-470, Brazil.
المصدر:	ACS chemical neuroscience [ACS Chem Neurosci] 2023 Dec 20; Vol. 14 (24), pp. 4298-4310. Date of Electronic Publication: 2023 Dec 04.
نوع المنشور:	Journal Article; Research Support, Non-U.S. Gov't
اللغة:	English
بيانات الدورية:	Publisher: American Chemical Society Country of Publication: United States NLM ID: 101525337 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1948-7193 (Electronic) Linking ISSN: 19487193 NLM ISO Abbreviation: ACS Chem Neurosci Subsets: MEDLINE
أسماء مطبوعة:	Original Publication: Washington, D.C. : American Chemical Society
مواضيع طبية MeSH:	Alzheimer Disease/pathology , Cognitive Dysfunction/chemically induced , Cognitive Dysfunction/drug therapy , Lignans/pharmacology , Neuroprotective Agents*/pharmacology, Mice ; Male ; Animals ; Amyloid beta-Peptides/metabolism ; Memantine/pharmacology ; Antioxidants/pharmacology ; Furans/pharmacology ; Anti-Inflammatory Agents/pharmacology ; Hippocampus/metabolism
مستخلص:	Alzheimer's disease (AD) is a neurodegenerative disorder caused by accumulation of amyloid-β oligomers (AβO) in the brain, neuroinflammation, oxidative stress, and cognitive decline. Grandisin, a tetrahydrofuran neolignan, exhibits relevant anti-inflammatory and antioxidant properties. Interestingly, grandisin-based compounds were shown to prevent AβO-induced neuronal death in vitro. However, no study has assessed the effect of these compounds on the AD animal model. This study focuses on a triazole grandisin analogue (TGA) synthesized using simplification and bioisosteric drug design, which resulted in improved potency and solubility compared with the parent compound. This study aimed to investigate the possible in vivo effects of TGA against AβO-induced AD. Male C57/Bl6 mice underwent stereotaxic intracerebroventricular AβO (90 μM) or vehicle injections. 24 h after surgery, animals received intraperitoneal treatment with TGA (1 mg/kg) or vehicle, administered on a 14 day schedule. One day after treatment completion, a novel object recognition task (NORT) was performed. Memantine (10 mg/kg) was administered as a positive control. NORT retention sessions were performed on days 8 and 16 after AβO injection. Immediately after retention sessions, animals were euthanized for cortex and hippocampus collection. Specimens were subjected to oxidative stress and cytokine analyses. TGA reduced the level of cortex/hippocampus lipoperoxidation and prevented cognitive impairment in AβO-injected mice. Additionally, TGA reduced tumor necrosis factor (TNF) and interferon-γ (IFN-γ) levels in the hippocampus. By contrast, memantine failed to prevent cortex/hippocampus lipid peroxidation, recognition memory decline, and AβO-induced increases in TNF and IFN-γ levels in the hippocampus. Thus, memantine was unable to avoid the AβO-induced persistent cognitive impairment. The results showed that TGA may prevent memory impairment by exerting antioxidant and anti-inflammatory effects in AβO-injected mice. Moreover, TGA exhibited a persistent neuroprotective effect compared to memantine, reflecting an innovative profile of this promising agent against neurodegenerative diseases, such as AD.
فهرسة مساهمة:	Keywords: Alzheimer’s disease; neuroprotection; oxidative stress; tetrahydrofuran neolignan derivative
المشرفين على المادة:	0 (Amyloid beta-Peptides) 53250-50-3 (grandisin) W8O17SJF3T (Memantine) 0 (Antioxidants) 0 (Lignans) 0 (Furans) 0 (Anti-Inflammatory Agents) 0 (Neuroprotective Agents)
تواريخ الأحداث:	Date Created: 20231204 Date Completed: 20231221 Latest Revision: 20240613
رمز التحديث:	20240614
DOI:	10.1021/acschemneuro.3c00443
PMID:	38048522
قاعدة البيانات:	MEDLINE

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تدمد:	1948-7193
DOI:	10.1021/acschemneuro.3c00443