scholarly journals Brain Glucose Transporters: Role in Pathogenesis and Potential Targets for the Treatment of Alzheimer’s Disease

2021 ◽  
Vol 22 (15) ◽  
pp. 8142
Author(s):  
Leszek Szablewski
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glucose Transporters ◽  
Energy Deficit ◽  
Main Risk Factor ◽  
Brain Glucose ◽  
Common Cause ◽  
Brain Energy ◽  
Glucose Hypometabolism

The most common cause of dementia, especially in elderly people, is Alzheimer’s disease (AD), with aging as its main risk factor. AD is a multifactorial neurodegenerative disease. There are several factors increasing the risk of AD development. One of the main features of Alzheimer’s disease is impairment of brain energy. Hypometabolism caused by decreased glucose uptake is observed in specific areas of the AD-affected brain. Therefore, glucose hypometabolism and energy deficit are hallmarks of AD. There are several hypotheses that explain the role of glucose hypometabolism in AD, but data available on this subject are poor. Reduced transport of glucose into neurons may be related to decreased expression of glucose transporters in neurons and glia. On the other hand, glucose transporters may play a role as potential targets for the treatment of AD. Compounds such as antidiabetic drugs, agonists of SGLT1, insulin, siRNA and liposomes are suggested as therapeutics. Nevertheless, the suggested targets of therapy need further investigations.

scholarly journals Possible Clues for Brain Energy Translation via Endolysosomal Trafficking of APP-CTFs in Alzheimer’s Disease

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Senthilkumar Sivanesan ◽  
Ravi Mundugaru ◽  
Jayakumar Rajadas
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Ketone Bodies ◽  
Brain Regions ◽  
Pentose Phosphate ◽  
Lactate Shuttle ◽  
Carboxy Terminal ◽  
Brain Energy

Vascular dysfunctions, hypometabolism, and insulin resistance are high and early risk factors for Alzheimer’s disease (AD), a leading neurological disease associated with memory decline and cognitive dysfunctions. Early defects in glucose transporters and glycolysis occur during the course of AD progression. Hypometabolism begins well before the onset of early AD symptoms; this timing implicates the vulnerability of hypometabolic brain regions to beta-secretase 1 (BACE-1) upregulation, oxidative stress, inflammation, synaptic failure, and cell death. Despite the fact that ketone bodies, astrocyte-neuron lactate shuttle, pentose phosphate pathway (PPP), and glycogenolysis compensate to provide energy to the starving AD brain, a considerable energy crisis still persists and increases during disease progression. Studies that track brain energy metabolism in humans, animal models of AD, and in vitro studies reveal striking upregulation of beta-amyloid precursor protein (β-APP) and carboxy-terminal fragments (CTFs). Currently, the precise role of CTFs is unclear, but evidence supports increased endosomal-lysosomal trafficking of β-APP and CTFs through autophagy through a vague mechanism. While intracellular accumulation of Aβ is attributed as both the cause and consequence of a defective endolysosomal-autophagic system, much remains to be explored about the other β-APP cleavage products. Many recent works report altered amino acid catabolism and expression of several urea cycle enzymes in AD brains, but the precise cause for this dysregulation is not fully explained. In this paper, we try to connect the role of CTFs in the energy translation process in AD brain based on recent findings.

scholarly journals Brain glucose transporters,O-GlcNAcylation and phosphorylation of tau in diabetes and Alzheimer’s disease

2009 ◽  
Vol 111 (1) ◽  
pp. 242-249 ◽  
Author(s):  
Ying Liu ◽  
Fei Liu ◽  
Inge Grundke-Iqbal ◽  
Khalid Iqbal ◽  
Cheng-Xin Gong
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glucose Transporters ◽  
Brain Glucose

scholarly journals Synchronous nonmonotonic changes in functional connectivity and white matter integrity in a rat model of sporadic Alzheimer’s disease

2020 ◽  
Author(s):  
Catarina Tristão Pereira ◽  
Yujian Diao ◽  
Ting Yin ◽  
Analina R da Silva ◽  
Bernard Lanz ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
White Matter ◽  
Functional Connectivity ◽  
Structure And Function ◽  
Acute Injury ◽  
Therapeutic Window ◽  
Brain Glucose ◽  
And Function ◽  
Glucose Hypometabolism

AbstractBrain glucose hypometabolism has been singled out as an important contributor and possibly main trigger to Alzheimer’s disease (AD). Intracerebroventricular injections of streptozotocin (icv-STZ) cause brain glucose hypometabolism without systemic diabetes. Here, a first-time longitudinal study of brain glucose metabolism, functional connectivity and white matter microstructure was performed in icv-STZ rats using PET and MRI. Histological markers of pathology were tested at an advanced stage of disease. STZ rats exhibited altered functional connectivity and intra-axonal damage and demyelination in brain regions typical of AD, in a temporal pattern of acute injury, transient recovery/compensation and chronic degeneration. In the context of sustained glucose hypometabolism, these nonmonotonic trends – also reported in behavioral studies of this animal model as well as in human AD – suggest a compensatory mechanism, possibly recruiting ketone bodies, that allows a partial and temporary repair of brain structure and function. The early acute phase could thus become a valuable therapeutic window to strengthen the recovery phase and prevent or delay chronic degeneration, to be considered both in preclinical and clinical studies of AD. In conclusion, this work reveals the consequences of brain insulin resistance on structure and function, highlights signature nonmonotonic trajectories in their evolution and proposes potent MRI-derived biomarkers translatable to human AD and diabetic populations.

The role of epsilon phenotype in brain glucose consumption in Alzheimer’s disease

2020 ◽  
Vol 34 (4) ◽  
pp. 254-262 ◽  
Author(s):  
Maria Ricci ◽  
Agostino Chiaravalloti ◽  
Alessandro Martorana ◽  
Giacomo Koch ◽  
Vincenzo De lucia ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glucose Consumption ◽  
Brain Glucose

P1-078: Reduced thiamine diphosphate level contributes to brain glucose hypometabolism and neurodegeneration in Alzheimer's disease

2015 ◽  
Vol 11 (7S_Part_8) ◽  
pp. P368-P368
Author(s):  
Shaoming Sang ◽  
Huimin Liu ◽  
Xiaoli Pan ◽  
Shumei Pan ◽  
Yun Wang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Thiamine Diphosphate ◽  
Brain Glucose ◽  
Glucose Hypometabolism
Sign in / Sign up

Export Citation Format

Share Document