Immunolabelling of hippocampal microvessel glucose transporter protein is reduced in Alzheimer's disease

1994 ◽  
Vol 425 (1) ◽  
Author(s):  
N. Horwood ◽  
D.C. Davies
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glucose Transporter ◽  
Transporter Protein

Brain glucose transporter protein 2 and sporadic Alzheimer’s disease

2010 ◽  
Vol 1 (3) ◽  
Author(s):  
Melita Šalković-Petrišić ◽  
Peter Riederer
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glucose Transporter ◽  
Glucose Utilization ◽  
Brain State ◽  
Sporadic Alzheimer’S Disease ◽  
Insulin Resistant ◽  
Transporter Protein ◽  
Clinical Syndromes ◽  
The Brain

AbstractSporadic Alzheimer’s disease (sAD) is associated with decreased glucose/energy metabolism in the brain. The majority of glucose utilization in the brain appears to be mediated through glucose transporter protein 1 and 3 (GLUT1 and GLUT3). Deficiency of GLUT1 and GLUT3 in the brain has been found in sAD patients post mortem; however this is not unique to the disease as it is associated with different clinical syndromes as well. In line with recent findings that insulin resistant brain state precedes and may possibly cause sAD, an experimental sAD model based on the central application of the streptozotocin (STZ-icv rat model), which is a selective GLUT2 substrate, has drawn attention to the possible significance of the brain GLUT2 in sAD etiopathogenesis. Important steps in the GLUT2 and sAD interplay are reviewed and discussed. It is concluded that increased vulnerability of GLUT2 expressing neurons may be involved in development of sAD.

scholarly journals Chenodeoxycholic Acid Ameliorates AlCl3-Induced Alzheimer’s Disease Neurotoxicity and Cognitive Deterioration via Enhanced Insulin Signaling in Rats

Molecules ◽  
2019 ◽  
Vol 24 (10) ◽  
pp. 1992 ◽  
Author(s):  
Firas H. Bazzari ◽  
Dalaal M. Abdallah ◽  
Hanan S. El-Abhar
Keyword(s):  
Alzheimer’S Disease ◽  
Insulin Resistance ◽  
Alzheimer's Disease ◽  
Chenodeoxycholic Acid ◽  
Insulin Signaling ◽  
Glucose Transporter ◽  
Farnesoid X Receptor ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Significant Difference

Insulin resistance is a major risk factor for Alzheimer’s disease (AD). Chenodeoxycholic acid (CDCA) and synthetic Farnesoid X receptor (FXR) ligands have shown promising outcomes in ameliorating insulin resistance associated with various medical conditions. This study aimed to investigate whether CDCA treatment has any potential in AD management through improving insulin signaling. Adult male Wistar rats were randomly allocated into three groups and treated for six consecutive weeks; control (vehicle), AD-model (AlCl3 50 mg/kg/day i.p) and CDCA-treated group (AlCl3 + CDCA 90 mg/kg/day p.o from day 15). CDCA improved cognition as assessed by Morris Water Maze and Y-maze tests and preserved normal histological features. Moreover, CDCA lowered hippocampal beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) and amyloid-beta 42 (Aβ42). Although no significant difference was observed in hippocampal insulin level, CDCA reduced insulin receptor substrate-1 phosphorylation at serine-307 (pSer307-IRS1), while increased protein kinase B (Akt) activation, glucose transporter type 4 (GLUT4), peroxisome proliferator-activated receptor gamma (PPARγ) and glucagon-like peptide-1 (GLP-1). Additionally, CDCA activated cAMP response element-binding protein (CREB) and enhanced brain-derived neurotrophic factor (BDNF). Ultimately, CDCA was able to improve insulin sensitivity in the hippocampi of AlCl3-treated rats, which highlights its potential in AD management.

scholarly journals Undiscovered Roles for Transthyretin: From a Transporter Protein to a New Therapeutic Target for Alzheimer’s Disease

2020 ◽  
Vol 21 (6) ◽  
pp. 2075 ◽  
Author(s):  
Tiago Gião ◽  
Joana Saavedra ◽  
Ellen Cotrina ◽  
Jordi Quintana ◽  
Jordi Llop ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Binding Protein ◽  
Retinol Binding Protein ◽  
Vascular Events ◽  
Aβ Peptides ◽  
Transporter Protein ◽  
Amyloid Aβ ◽  
Cellular Pathways

Transthyretin (TTR), an homotetrameric protein mainly synthesized by the liver and the choroid plexus, and secreted into the blood and the cerebrospinal fluid, respectively, has been specially acknowledged for its functions as a transporter protein of thyroxine and retinol (the latter through binding to the retinol-binding protein), in these fluids. Still, this protein has managed to stay in the spotlight as it has been assigned new and varied functions. In this review, we cover knowledge on novel TTR functions and the cellular pathways involved, spanning from neuroprotection to vascular events, while emphasizing its involvement in Alzheimer’s disease (AD). We describe details of TTR as an amyloid binding protein and discuss its interaction with the amyloid Aβ peptides, and the proposed mechanisms underlying TTR neuroprotection in AD. We also present the importance of translating advances in the knowledge of the TTR neuroprotective role into drug discovery strategies focused on TTR as a new target in AD therapeutics.

scholarly journals Blood-brain barrier–penetrating siRNA nanomedicine for Alzheimer’s disease therapy

2020 ◽  
Vol 6 (41) ◽  
pp. eabc7031 ◽  
Author(s):  
Yutong Zhou ◽  
Feiyan Zhu ◽  
Yang Liu ◽  
Meng Zheng ◽  
Yibin Wang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Blood Brain Barrier ◽  
Glucose Transporter ◽  
Amyloid Β ◽  
Cognitive Capacity ◽  
Brain Barrier ◽  
Great Promise ◽  
Glucose Transporter 1 ◽  
Blood Brain

Toxic aggregated amyloid-β accumulation is a key pathogenic event in Alzheimer’s disease (AD), which derives from amyloid precursor protein (APP) through sequential cleavage by BACE1 (β-site APP cleavage enzyme 1) and γ-secretase. Small interfering RNAs (siRNAs) show great promise for AD therapy by specific silencing of BACE1. However, lack of effective siRNA brain delivery approaches limits this strategy. Here, we developed a glycosylated “triple-interaction” stabilized polymeric siRNA nanomedicine (Gal-NP@siRNA) to target BACE1 in APP/PS1 transgenic AD mouse model. Gal-NP@siRNA exhibits superior blood stability and can efficiently penetrate the blood-brain barrier (BBB) via glycemia-controlled glucose transporter-1 (Glut1)–mediated transport, thereby ensuring that siRNAs decrease BACE1 expression and modify relative pathways. Noticeably, Gal-NP@siBACE1 administration restored the deterioration of cognitive capacity in AD mice without notable side effects. This “Trojan horse” strategy supports the utility of RNA interference therapy in neurodegenerative diseases.

Reduced glucose transporter-1 in brain derived circulating endothelial cells in mild Alzheimer’s disease patients

2018 ◽  
Vol 1678 ◽  
pp. 304-309 ◽  
Author(s):  
Petra Vogelsang ◽  
Lasse Melvaer Giil ◽  
Anders Lund ◽  
Christian A. Vedeler ◽  
Anagha P. Parkar ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Endothelial Cells ◽  
Glucose Transporter ◽  
Circulating Endothelial Cells ◽  
Glucose Transporter 1

scholarly journals Visualization of reactive astrocytes in living brain of Alzheimer’s disease patient

2021 ◽  
Author(s):  
Min-Ho Nam ◽  
Hae Young Ko ◽  
Sangwon Lee ◽  
Yongmin Mason Park ◽  
Seung Jae Hyeon ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glucose Transporter ◽  
Disease Patient ◽  
Ct Imaging ◽  
Reactive Astrocytes ◽  
Monocarboxylate Transporter ◽  
Diagnostic Strategy ◽  
Monocarboxylate Transporter 1 ◽  
Pet Ct

AbstractAn early appearance of reactive astrocytes is a hallmark of Alzheimer’s disease (AD)1,2, providing a substrate for early diagnostic neuroimaging targets. However, there is no clinically validated neuroimaging probe to visualize the reactive astrogliosis in the human brain in vivo. Here, we report that PET/CT imaging with 11C-acetate and 18F-fluorodeoxyglucose (18F-FDG) functionally visualizes the reactive astrocyte-mediated neuronal hypometabolism in the brains with neuroinflammation and AD. We demonstrate that reactive astrocytes excessively absorb acetate through elevated monocarboxylate transporter-1 (MCT1), leading to aberrant GABA synthesis and release which suppresses neuronal glucose uptake through decreased glucose transporter-3 (GLUT3) in both animal and human brains. We propose the non-invasive functional PET/CT imaging for astrocytic acetate-hypermetabolism and neuronal glucose-hypometabolism as an advanced diagnostic strategy for early stages of AD.

scholarly journals Putative Involvement of Endocrine Disruptors in the Alzheimer's disease Via the Insulin-Regulated Aminopeptidase / GLUT4 Pathway

2020 ◽  
Vol 18 ◽  
Author(s):  
María Jesús Ramírez-Expósito ◽  
Jose Manuel Martínez-Martos ◽  
Vanesa Cantón-Habas ◽  
María del Pilar Carrera González
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Surface ◽  
Glucose Transporter ◽  
Cell Function ◽  
Sensory Information ◽  
Inhibitory Effect ◽  
Pharmacological Intervention ◽  
Pancreatic Cell ◽  
The One

: It has been well established that there is a connection between type II diabetes (DMTII) and Alzheimer's disease (AD). In fact, the increase in AD incidence may be an emerging complication of DMTII. Both pathologies are related to estradiol (E2) exposure; on the one hand, estrogen receptors (ER) are emerging as important modulators of glucose homeostasis through ß-pancreatic cell function; on the other hand, brain bioenergetic and cognitive deficits have been related to the down regulation of brain ERs, contributing to women ageing and AD susceptibility, both related to the reduction in estradiol levels and the deficits in brain metabolism. Here we discuss that environmental contaminants with estrogenic capacity such as bisphenol A (BPA) could develop pharmacological effects similar to those of E2, which could affect ß-pancreatic cell function by increasing the biosynthesis of glucose-induced insulin after extranuclear ER binding. BPA-induced hyperinsulinemia would promote the translocation of glucose transporter 4 (GLUT4) which is located next to insulin-regulated aminopeptidase (IRAP) in intracellular vesicles. In insulin-responsive tissues, IRAP and GLUT 4 are routed together to the cell surface after insulin stimulation. IRAP is also the angiotensin IV (AngIV) receptor, and AngIV associates the brain reninangiotensin system (bRAS) with AD, since AngIV is related to learning, memory, emotional responses, and processing of sensory information not only through its inhibitory effect on IRAP but also through the stimulation of glucose uptake by increasing the presence of IRAP/GLUT4 at the cell surface. Thus, the IRAP/GLUT4 pathway is an emerging target for the pharmacological intervention against AD.

P2-081: CREB regulates the expression of neuronal glucose transporter 3: A mechanism leading to impaired brain glucose uptake in Alzheimer's disease

2012 ◽  
Vol 8 (4S_Part_8) ◽  
pp. P292-P292
Author(s):  
Nana Jin ◽  
Wei Qian ◽  
Xiaomin Yin ◽  
Khalid Iqbal ◽  
Inge Grundke-Iqbal ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glucose Uptake ◽  
Glucose Transporter ◽  
Brain Glucose
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