Therapeutic Potential of MCC950 in Restoring Autophagy and Cognitive Function in STZ-Induced Rat Model of Alzheimer's Disease.

IF 4.6 2区医学 Q1 NEUROSCIENCES

Molecular Neurobiology Pub Date : 2025-05-01 Epub Date: 2024-12-20 DOI:10.1007/s12035-024-04662-y

Abdul Naeem, Arshi Waseem, Mohsin Ali Khan, Avril Ab Robertson, Syed Shadab Raza

{"title":"Therapeutic Potential of MCC950 in Restoring Autophagy and Cognitive Function in STZ-Induced Rat Model of Alzheimer's Disease.","authors":"Abdul Naeem, Arshi Waseem, Mohsin Ali Khan, Avril Ab Robertson, Syed Shadab Raza","doi":"10.1007/s12035-024-04662-y","DOIUrl":null,"url":null,"abstract":"<p><p>Alzheimer's disease (AD) is currently the seventh leading cause of death worldwide. In this study, we explored the critical role of autophagy in AD pathology using a streptozotocin (STZ)-induced AD model in Wistar rats. The experimental groups included sham, STZ-induced AD, and STZ + MCC950-treated animals. Our findings revealed that administering two doses of STZ (3 mg/kg) intracerebroventricular at the interval of 48 h (on days 0 and 2), triggered autophagy, as evidenced by elevated levels of autophagy markers such as LC3II, ULK1, Beclin1, Ambra1, Cathepsin B, and a reduction in p62 levels. Behavioral assessments, including the water maze and novel object recognition tests, confirmed cognitive deficits and memory impairment, while the open-field test indicated increased anxiety in STZ-induced AD rats. In particular, treating the STZ-induced AD group with MCC950 (50 mg/kg) decreased the overexpression of autophagy-related proteins, which was consistent with better behavioral outcomes and lower anxiety. Overall, this study highlights new insights into AD pathophysiology and suggests potential therapeutic avenues.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"6041-6058"},"PeriodicalIF":4.6000,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Neurobiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s12035-024-04662-y","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/12/20 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}

引用次数: 0

Abstract

Alzheimer's disease (AD) is currently the seventh leading cause of death worldwide. In this study, we explored the critical role of autophagy in AD pathology using a streptozotocin (STZ)-induced AD model in Wistar rats. The experimental groups included sham, STZ-induced AD, and STZ + MCC950-treated animals. Our findings revealed that administering two doses of STZ (3 mg/kg) intracerebroventricular at the interval of 48 h (on days 0 and 2), triggered autophagy, as evidenced by elevated levels of autophagy markers such as LC3II, ULK1, Beclin1, Ambra1, Cathepsin B, and a reduction in p62 levels. Behavioral assessments, including the water maze and novel object recognition tests, confirmed cognitive deficits and memory impairment, while the open-field test indicated increased anxiety in STZ-induced AD rats. In particular, treating the STZ-induced AD group with MCC950 (50 mg/kg) decreased the overexpression of autophagy-related proteins, which was consistent with better behavioral outcomes and lower anxiety. Overall, this study highlights new insights into AD pathophysiology and suggests potential therapeutic avenues.

查看原文本刊更多论文

MCC950 在 STZ 诱导的阿尔茨海默病大鼠模型中恢复自噬和认知功能的治疗潜力

阿尔茨海默病（AD）目前是全球第七大死因。在这项研究中，我们利用链脲佐菌素（STZ）诱导的Wistar大鼠AD模型，探讨自噬在AD病理中的关键作用。实验组分为假手术组、STZ诱导AD组和STZ + mcc950处理组。我们的研究结果显示，间隔48小时（第0天和第2天）给药两剂STZ （3mg /kg）脑室内可触发自噬，自噬标志物如LC3II、ULK1、Beclin1、Ambra1、Cathepsin B水平升高，p62水平降低。行为评估，包括水迷宫和新物体识别测试，证实了认知缺陷和记忆障碍，而开放场地测试表明stz诱导的AD大鼠焦虑增加。特别是，用MCC950 （50 mg/kg）治疗stz诱导的AD组，可以降低自噬相关蛋白的过表达，这与更好的行为结果和更低的焦虑水平是一致的。总的来说，这项研究突出了对阿尔茨海默病病理生理学的新见解，并提出了潜在的治疗途径。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Molecular Neurobiology 医学-神经科学

CiteScore

9.00

自引率

2.00%

发文量

480

审稿时长

1 months

期刊介绍： Molecular Neurobiology is an exciting journal for neuroscientists needing to stay in close touch with progress at the forefront of molecular brain research today. It is an especially important periodical for graduate students and "postdocs," specifically designed to synthesize and critically assess research trends for all neuroscientists hoping to stay active at the cutting edge of this dramatically developing area. This journal has proven to be crucial in departmental libraries, serving as essential reading for every committed neuroscientist who is striving to keep abreast of all rapid developments in a forefront field. Most recent significant advances in experimental and clinical neuroscience have been occurring at the molecular level. Until now, there has been no journal devoted to looking closely at this fragmented literature in a critical, coherent fashion. Each submission is thoroughly analyzed by scientists and clinicians internationally renowned for their special competence in the areas treated.