Insights from Drosophila on Aβ- and tau-induced mitochondrial dysfunction: mechanisms and tools.
Insights from Drosophila on Aβ- and tau-induced mitochondrial dysfunction: mechanisms and tools.
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DOI：
10.3389/fnins.2023.1184080
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发表时间：
2023
影响因子：
4.3
通讯作者：
Rincon-Limas, Diego E.
中科院分区：
文献类型：
--
作者：
Varte, Vanlalrinchhani;Munkelwitz, Jeremy W.;Rincon-Limas, Diego E.
阿尔茨海默病（Alzheimer's disease，AD）是世界范围内老年人中最常见的神经退行性痴呆。可悲的是，由于疾病的多因素复杂性，没有可用于治疗的疾病修饰疗法。AD的病理特征是淀粉样蛋白β（Aβ）的细胞外沉积和由过度磷酸化的tau组成的细胞内神经元缠结。越来越多的证据表明，Aβ也在细胞内蓄积，这可能导致AD中观察到的病理性线粒体功能障碍。根据线粒体级联假说，线粒体功能障碍先于临床衰退，因此靶向线粒体可能导致新的治疗策略。不幸的是，连接线粒体功能障碍与AD的确切机制在很大程度上是未知的。在这篇综述中，我们将讨论果蝇是如何有助于回答该领域的机制问题，从线粒体氧化应激和钙调节失调，线粒体自噬和线粒体融合和分裂。特别是，我们将强调转基因果蝇中Aβ和tau蛋白引起的特定线粒体损伤，并将讨论可用于研究这种灵活生物体中线粒体生物学的各种遗传工具和传感器。还将考虑机会领域和未来方向。
Alzheimer’s disease (AD) is the most prevalent neurodegenerative dementia in older adults worldwide. Sadly, there are no disease-modifying therapies available for treatment due to the multifactorial complexity of the disease. AD is pathologically characterized by extracellular deposition of amyloid beta (Aβ) and intracellular neurofibrillary tangles composed of hyperphosphorylated tau. Increasing evidence suggest that Aβ also accumulates intracellularly, which may contribute to the pathological mitochondrial dysfunction observed in AD. According with the mitochondrial cascade hypothesis, mitochondrial dysfunction precedes clinical decline and thus targeting mitochondria may result in new therapeutic strategies. Unfortunately, the precise mechanisms connecting mitochondrial dysfunction with AD are largely unknown. In this review, we will discuss how the fruit fly Drosophila melanogaster is contributing to answer mechanistic questions in the field, from mitochondrial oxidative stress and calcium dysregulation to mitophagy and mitochondrial fusion and fission. In particular, we will highlight specific mitochondrial insults caused by Aβ and tau in transgenic flies and will also discuss a variety of genetic tools and sensors available to study mitochondrial biology in this flexible organism. Areas of opportunity and future directions will be also considered.
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DOI：
10.1016/j.nicl.2017.04.001
发表时间：
2017
期刊：
NeuroImage. Clinical
影响因子：
--
作者：
Ramos Bernardes da Silva Filho S;Oliveira Barbosa JH;Rondinoni C;Dos Santos AC;Garrido Salmon CE;da Costa Lima NK;Ferriolli E;Moriguti JC
通讯作者：
Moriguti JC
影响因子：
3.5
作者：
Abtahi, Seyedeh Leila;Masoudi, Raheleh;Haddadi, Mohammad
通讯作者：
Haddadi, Mohammad
DOI：
10.1016/s0140-6736(20)32205-4
发表时间：
2021-04-24
期刊：
Lancet (London, England)
影响因子：
--
作者：
Scheltens P;De Strooper B;Kivipelto M;Holstege H;Chételat G;Teunissen CE;Cummings J;van der Flier WM
通讯作者：
van der Flier WM
影响因子：
15.1
作者：
Allen M;Zou F;Chai HS;Younkin CS;Miles R;Nair AA;Crook JE;Pankratz VS;Carrasquillo MM;Rowley CN;Nguyen T;Ma L;Malphrus KG;Bisceglio G;Ortolaza AI;Palusak R;Middha S;Maharjan S;Georgescu C;Schultz D;Rakhshan F;Kolbert CP;Jen J;Sando SB;Aasly JO;Barcikowska M;Uitti RJ;Wszolek ZK;Ross OA;Petersen RC;Graff-Radford NR;Dickson DW;Younkin SG;Ertekin-Taner N
通讯作者：
Ertekin-Taner N
影响因子：
3.3
作者：
Aksenov, MY;Aksenova, MV;Markesbery, WR
通讯作者：
Markesbery, WR