A Systematic Review of Glucose Transport Alterations in Alzheimer's Disease.
A Systematic Review of Glucose Transport Alterations in Alzheimer's Disease.
复制标题
对阿尔茨海默氏病的葡萄糖转运改变的系统评价。
DOI：
10.3389/fnins.2021.626636
复制
发表时间：
2021
影响因子：
4.3
通讯作者：
Dickie BR
中科院分区：
文献类型：
--
作者：
Kyrtata N;Emsley HCA;Sparasci O;Parkes LM;Dickie BR
阿尔茨海默病（Alzheimer's disease，AD）是一种以脑葡萄糖代谢低下为特征的疾病。低代谢可能部分是由于血脑屏障（BBB）和跨星形胶质细胞和神经元细胞膜的葡萄糖转运减少。葡萄糖转运蛋白（GLUT）是负责将葡萄糖从血流移动到其代谢的实质细胞的完整膜蛋白，并且有证据表明血管和非血管GLUT在AD脑中发生改变，这是一个可能使脑葡萄糖饥饿并加速认知衰退的过程。在这里，我们回顾文献中的葡萄糖转运改变AD从人类和啮齿动物的研究。研究方法：检索了EMBASE和MEDLINE数据库中1946年1月1日至2020年11月1日期间发表的文献，检索词为“葡萄糖转运蛋白”和“阿尔茨海默病”。纳入了人类和啮齿动物研究，但排除了综述、信函和体外研究。结果：确定了43项符合纳入标准的研究，包括人类（23项研究）和啮齿动物（20项研究）。尸检研究表明，在AD大脑的海马体和皮质中，GLUT 1和GLUT 3的一致减少，大脑的区域与AD病理学密切相关。在AD和人类AD的啮齿动物模型中的示踪剂研究也表现出葡萄糖和葡萄糖类似物进入大脑的摄取减少，支持这些发现。纵向啮齿动物研究清楚地表明，GLUT 1和GLUT 3的变化仅发生在淀粉样蛋白-β病理学存在之后，并且几项研究表明淀粉样蛋白-β本身可能是GLUT变化的原因。此外，来自人类和啮齿动物研究的证据表明，GLUT消耗对大脑功能有严重影响。少数研究表明GLUT 2和GLUT 12在AD中增加。抗糖尿病药物改善AD受试者的葡萄糖转运能力。结论：在AD患者和啮齿动物模型中，海马和皮质区域的GLUT 1和GLUT 3减少，可能是由这些区域中高水平的淀粉样蛋白β引起的。GLUT 3减少似乎先于临床症状发作。GLUT 2和GLUT 12似乎增加，可能具有代偿作用。改变抗糖尿病药物的用途以改变葡萄糖转运在AD的人体研究中显示出有希望的结果。
Introduction: Alzheimer's disease (AD) is characterized by cerebral glucose hypometabolism. Hypometabolism may be partly due to reduced glucose transport at the blood-brain barrier (BBB) and across astrocytic and neuronal cell membranes. Glucose transporters (GLUTs) are integral membrane proteins responsible for moving glucose from the bloodstream to parenchymal cells where it is metabolized, and evidence indicates vascular and non-vascular GLUTs are altered in AD brains, a process which could starve the brain of glucose and accelerate cognitive decline. Here we review the literature on glucose transport alterations in AD from human and rodent studies. Methods: Literature published between 1st January 1946 and 1st November 2020 within EMBASE and MEDLINE databases was searched for the terms “glucose transporters” AND “Alzheimer's disease”. Human and rodent studies were included while reviews, letters, and in-vitro studies were excluded. Results: Forty-three studies fitting the inclusion criteria were identified, covering human (23 studies) and rodent (20 studies). Post-mortem studies showed consistent reductions in GLUT1 and GLUT3 in the hippocampus and cortex of AD brains, areas of the brain closely associated with AD pathology. Tracer studies in rodent models of AD and human AD also exhibit reduced uptake of glucose and glucose-analogs into the brain, supporting these findings. Longitudinal rodent studies clearly indicate that changes in GLUT1 and GLUT3 only occur after amyloid-β pathology is present, and several studies indicate amyloid-β itself may be responsible for GLUT changes. Furthermore, evidence from human and rodent studies suggest GLUT depletion has severe effects on brain function. A small number of studies show GLUT2 and GLUT12 are increased in AD. Anti-diabetic medications improved glucose transport capacity in AD subjects. Conclusions: GLUT1 and GLUT3 are reduced in hippocampal and cortical regions in patients and rodent models of AD, and may be caused by high levels of amyloid-β in these regions. GLUT3 reductions appear to precede the onset of clinical symptoms. GLUT2 and GLUT12 appear to increase and may have a compensatory role. Repurposing anti-diabetic drugs to modify glucose transport shows promising results in human studies of AD.
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DOI：
10.1016/j.ijdevneu.2014.08.003
发表时间：
2014-11
期刊：
International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience
影响因子：
--
作者：
Cohen SS;Powers BR;Lerch-Gaggl A;Teng RJ;Konduri GG
通讯作者：
Konduri GG
影响因子：
4.8
作者：
Biswas, Joyshree;Gupta, Sonam;Singh, Sarika
通讯作者：
Singh, Sarika
影响因子：
4
作者：
Chua, Li-Min;Lim, Mei-Li;Wong, Boon-Seng
通讯作者：
Wong, Boon-Seng
影响因子：
2.9
作者：
CARRUTHERS, A;HELGERSON, AL
通讯作者：
HELGERSON, AL
影响因子：
29
作者：
Hanseeuw, Bernard J.;Betensky, Rebecca A.;Johnson, Keith
通讯作者：
Johnson, Keith