Altered substrate metabolism in neurodegenerative disease: new insights from metabolic imaging.
Altered substrate metabolism in neurodegenerative disease: new insights from metabolic imaging.
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DOI：
10.1186/s12974-021-02305-w
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发表时间：
2021-10-28
影响因子：
9.3
通讯作者：
Bruce KD
中科院分区：
文献类型：
--
作者：
Cleland NRW;Al-Juboori SI;Dobrinskikh E;Bruce KD
神经退行性疾病（ND），如阿尔茨海默病（AD）、帕金森病（PD）和多发性硬化症（MS），是相对常见和破坏性的神经系统疾病。例如，在美国有600万人患有AD，预计到2030年这个数字将增长到1400万。重要的是，AD、PD和MS的特征都是缺乏能够逆转或阻止疾病进展的真正的疾病修饰疗法。此外，大多数ND的现有护理标准仅针对疾病的症状。因此，非常需要针对疾病神经发病机制的替代策略。最近的研究表明，神经元和神经胶质的代谢改变通常在AD，PD和MS中观察到，并导致细胞功能的变化，这些变化可以在疾病发作和进展之前或预防疾病发作和进展。具体而言，单细胞RNAseq研究表明，AD进展与小胶质细胞的代谢表型密切相关，小胶质细胞是大脑的关键免疫效应细胞。然而，这些分析涉及将细胞从其天然环境中取出并在体外进行测量，从而影响代谢状态。因此，能够准确评估细胞特异性原位代谢的技术方法有可能改变我们对AD驱动机制的理解。在这里，我们回顾了我们目前的理解代谢在神经元和神经胶质细胞在稳态和疾病。我们还评估了代谢成像的最新进展，并讨论了新兴的方式，如荧光寿命成像显微镜（FLIM）有可能确定如何代谢扰动可能会推动ND的进展。最后，我们建议FLIM提供的大脑代谢的时间，区域和细胞特异性特征将是合理设计代谢为重点的干预措施，延迟甚至预防ND的关键的第一步。
Neurodegenerative diseases (NDs), such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and multiple sclerosis (MS), are relatively common and devastating neurological disorders. For example, there are 6 million individuals living with AD in the United States, a number that is projected to grow to 14 million by the year 2030. Importantly, AD, PD and MS are all characterized by the lack of a true disease-modifying therapy that is able to reverse or halt disease progression. In addition, the existing standard of care for most NDs only addresses the symptoms of the disease. Therefore, alternative strategies that target mechanisms underlying the neuropathogenesis of disease are much needed. Recent studies have indicated that metabolic alterations in neurons and glia are commonly observed in AD, PD and MS and lead to changes in cell function that can either precede or protect against disease onset and progression. Specifically, single-cell RNAseq studies have shown that AD progression is tightly linked to the metabolic phenotype of microglia, the key immune effector cells of the brain. However, these analyses involve removing cells from their native environment and performing measurements in vitro, influencing metabolic status. Therefore, technical approaches that can accurately assess cell-specific metabolism in situ have the potential to be transformative to our understanding of the mechanisms driving AD. Here, we review our current understanding of metabolism in both neurons and glia during homeostasis and disease. We also evaluate recent advances in metabolic imaging, and discuss how emerging modalities, such as fluorescence lifetime imaging microscopy (FLIM) have the potential to determine how metabolic perturbations may drive the progression of NDs. Finally, we propose that the temporal, regional, and cell-specific characterization of brain metabolism afforded by FLIM will be a critical first step in the rational design of metabolism-focused interventions that delay or even prevent NDs.
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影响因子：
4.2
作者：
Beydoun MA;Boueiz A;Abougergi MS;Kitner-Triolo MH;Beydoun HA;Resnick SM;O'Brien R;Zonderman AB
通讯作者：
Zonderman AB
影响因子：
6.2
作者：
Amaral AI;Hadera MG;Tavares JM;Kotter MR;Sonnewald U
通讯作者：
Sonnewald U
影响因子：
10.4
作者：
Brown, Rebecca C;Lockwood, Alan H;Sonawane, Babasaheb R
通讯作者：
Sonawane, Babasaheb R
DOI：
10.1016/b978-0-12-814395-7.00009-x
发表时间：
2020-01-01
期刊：
HANDBOOK OF RADIOACTIVITY ANALYSIS, VOL 2: RADIOANALYTICAL APPLICATIONS, 4TH EDITION
影响因子：
--
作者：
Barthe, Nicole;Maitrejean, Serge;Cardona, Ana
通讯作者：
Cardona, Ana
影响因子：
4.2
作者：
Amtul, Zareen;Uhrig, Markus;Beyreuther, Konrad
通讯作者：
Beyreuther, Konrad