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

Szablewski, Leszek

doi:10.3390/ijms22158142

Cited by 47 publications

(39 citation statements)

References 163 publications

(232 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, the female sex [ 28 ], and cardiovascular risk factors such as stroke, poorly controlled high blood pressure, hypercholesterolemia, obesity, and diabetes are suggested to be among the potential predisposing factors [ 25 , 28 , 35 ]. Indeed, AD could be considered a central metabolic disease due to glucose hypometabolism [ 38 , 39 ], associated with impaired insulin and insulin-like growth factor (IGF) signaling pathways in the brain, which are physiologically involved in energy production and neuronal survival and plasticity, and therefore play a key role in cognition and memory [ 40 , 41 ]. These metabolic disruptions occur years before the onset of AD [ 42 ] and worsen with AD progression [ 40 ].…”

Section: Introductionmentioning

confidence: 99%

Type 2 Diabetes Mellitus and Alzheimer’s Disease: Shared Molecular Mechanisms and Potential Common Therapeutic Targets

Hamzé

Delangre

Tolu

et al. 2022

IJMS

View full text Add to dashboard Cite

The global prevalence of diabetes mellitus and Alzheimer’s disease is increasing alarmingly with the aging of the population. Numerous epidemiological data suggest that there is a strong association between type 2 diabetes and an increased risk of dementia. These diseases are both degenerative and progressive and share common risk factors. The amyloid cascade plays a key role in the pathophysiology of Alzheimer’s disease. The accumulation of amyloid beta peptides gradually leads to the hyperphosphorylation of tau proteins, which then form neurofibrillary tangles, resulting in neurodegeneration and cerebral atrophy. In Alzheimer’s disease, apart from these processes, the alteration of glucose metabolism and insulin signaling in the brain seems to induce early neuronal loss and the impairment of synaptic plasticity, years before the clinical manifestation of the disease. The large amount of evidence on the existence of insulin resistance in the brain during Alzheimer’s disease has led to the description of this disease as “type 3 diabetes”. Available animal models have been valuable in the understanding of the relationships between type 2 diabetes and Alzheimer’s disease, but to date, the mechanistical links are poorly understood. In this non-exhaustive review, we describe the main molecular mechanisms that may link these two diseases, with an emphasis on impaired insulin and IGF-1 signaling. We also focus on GSK3β and DYRK1A, markers of Alzheimer’s disease, which are also closely associated with pancreatic β-cell dysfunction and type 2 diabetes, and thus may represent common therapeutic targets for both diseases.

show abstract

Section: Introductionmentioning

confidence: 99%

Type 2 Diabetes Mellitus and Alzheimer’s Disease: Shared Molecular Mechanisms and Potential Common Therapeutic Targets

Hamzé

Delangre

Tolu

et al. 2022

IJMS

View full text Add to dashboard Cite

show abstract

“…Glucose is transported into brain cells via members of the GLUT family. GLUT-3 is primarily expressed in neurons, while GLUT-1 gene expression is limited to ECs in the healthy brain ( 29 ) and regulates glucose transport into the brain ( 30 , 31 ). Two subtypes of GLUT-1, a 55 kDa isoform in brain ECs and a 45 kDa isoform in adjacent astrocytes, have been reported previously ( 32 ).…”

Section: Discussionmentioning

confidence: 99%

Tanshinone IIA regulates expression of glucose transporter 1 via activation of the HIF‑1α signaling pathway

et al. 2022

View full text Add to dashboard Cite

Tanshinone IIA (Tan 2A) is a lipid-soluble compound extracted from the Chinese herb Danshen (Salvia miltiorrhiza Bunge). It protects neuron and microvascular endothelial cells against hypoxia/ischemia both in vitro and in vivo however the mechanism is not fully known. Glucose transporter 1 (GLUT-1) is ubiquitously expressed in all types of tissue in the human body and serves important physiological functions due to its glucose uptake ability. The present study evaluated the role of Tan 2A in regulating GLUT-1 expression and its potential mechanism. RT-PCR and western Blot were used to detect the expression of GLUT-1. Si RNA mediated knockdown and CHIP assay were used to explore the mechanism of Tan 2A on GLUT-1expression. Tan 2A treatment induced expression of GLUT-1 and subsequently increased glucose uptake in endothelial cells (ECs). Furthermore, mRNA expression levels of vascular endothelial cell growth factor, BCL2 interacting protein 3 and enolase 2, which are target genes for hypoxia-inducible factor-1α (HIF-1α), were significantly upregulated by Tan 2A. Co-immunoprecipitation demonstrated that Tan 2A markedly increased the association of HIF-1α with recombination signal-binding protein for immunoglobulin κJ region (RBPJκ). Moreover, knockdown of HIF-1α and RBPJκ significantly reversed the regulatory effect of Tan 2A on mRNA expression levels of these genes in ECs. The results of the present study suggested that HIF-1α partially mediated the regulatory effect of Tan 2A on GLUT-1 expression in ECs. Therefore, GLUT-1 may be a potential therapeutic target for Tan 2A.

show abstract

“…Another common occurrence for several neurodegenerative diseases is a disturbance in glucose metabolism and the function and expression of glucose transporters. For example, hypometabolism of glucose due to a decrease in expression of glucose transporters in the brain occurs in Alzheimer's disease [97]. Similarly, energy and glucose metabolism disturbances are suggested to play a role in the development of Huntington's disease pathology [98].…”

Section: Punicic Acid Induced a Higher Expression Of Glut4mentioning

confidence: 99%

“…GLUT4 is an insulin-sensitive glucose transporter expressed in the hypothalamus, sensorimotor cortex, hippocampus, and pituitary. Its physiological role is unknown, but some of its suggested functions are its involvement in glucose sensing, the insulin modulation of glucose transport in distinct brain areas, and the transport of glucose, in case of high demand, to the motor neurons [97,98].…”

Section: Punicic Acid Induced a Higher Expression Of Glut4mentioning

confidence: 99%

Punicic Acid and Its Role in the Prevention of Neurological Disorders: A Review

Guerra-Vázquez

Martínez-Ávila

Guajardo‐Flores

et al. 2022

Foods

View full text Add to dashboard Cite

Millions of people worldwide are affected by neurodegenerative diseases (NDs). NDs are characterized by progressive damage and death of nerve cells accompanied by high levels of inflammatory biomarkers and oxidative stress conditions. Punicic acid, the main bioactive component of pomegranate (Punica granatum) seed oil, is an omega-5 isomer of conjugated α-linoleic acid that has shown strong anti-oxidative and anti-inflammatory effects that contributes towards its positive effect against a wide arrange of diseases. Punicic acid decreases oxidative damage and inflammation by increasing the expression of peroxisome proliferator-activated receptors. In addition, it can reduce beta-amyloid deposits formation and tau hyperphosphorylation by increasing the expression of GLUT4 protein and the inhibition of calpain hyperactivation. Microencapsulated pomegranate, with high levels of punicic acid, increases antioxidant PON1 activity in HDL. Likewise, encapsulated pomegranate formulations with high levels of punicic acid have shown an increase in the antioxidant PON1 activity in HDL. Because of the limited brain permeability of punicic acid, diverse delivery formulations have been developed to enhance the biological activity of punicic acid in the brain, diminishing neurological disorders symptoms. Punicic acid is an important nutraceutical compound in the prevention and treatment of neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s disease.

show abstract

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

Cited by 47 publications

References 163 publications

Type 2 Diabetes Mellitus and Alzheimer’s Disease: Shared Molecular Mechanisms and Potential Common Therapeutic Targets

Type 2 Diabetes Mellitus and Alzheimer’s Disease: Shared Molecular Mechanisms and Potential Common Therapeutic Targets

Tanshinone IIA regulates expression of glucose transporter 1 via activation of the HIF‑1α signaling pathway

Punicic Acid and Its Role in the Prevention of Neurological Disorders: A Review

Contact Info

Product

Resources

About