Modification of membrane lipids protects neurons against insulin resistance in models of Alzheimer’s disease

e-Neuroforum ◽  
2017 ◽  
Vol 23 (4) ◽  
Author(s):  
Viola Nordström ◽  
Silke Herzer
Keyword(s):  
Alzheimer’S Disease ◽  
Insulin Resistance ◽  
Alzheimer's Disease ◽  
Amyloid Fibrils ◽  
Membrane Lipids ◽  
Insulin Receptors ◽  
Amyloid Oligomers ◽  
The Central Nervous System ◽  
Β Amyloid ◽  
Neuronal Insulin Resistance

AbstractAlzheimer’s disease is a degenerative disease of the central nervous system, which leads to severe deficits in memory and orientation by a progressive loss of neurons and synapses. Soluble β-amyloid oligomers are highly neurotoxic precursors of β-amyloid fibrils that accumulate in Alzheimer’s disease. Binding of β-amyloid oligomers to synaptic insulin receptors leads to neuronal insulin resistance, which significantly contributes to cognitive impairments.Insulin receptors are located in the cell membrane, which consists of a lipid bilayer and contains high amounts of glycosylated lipids, the so-called gangliosides. Gangliosides regulate insulin receptor activity via dynamic molecular interactions and facilitate the β-amyloid oligomer-induced insulin resistance. Thus, inhibiting ganglioside biosynthesis can protect neurons from the detrimental effects of β-amyloid oligomers.

scholarly journals Molecular Structure of β-Amyloid Fibrils in Alzheimer’s Disease Brain Tissue

Cell ◽  
2013 ◽  
Vol 154 (6) ◽  
pp. 1257-1268 ◽  
Author(s):  
Jun-Xia Lu ◽  
Wei Qiang ◽  
Wai-Ming Yau ◽  
Charles D. Schwieters ◽  
Stephen C. Meredith ◽  
...  
Keyword(s):  
Molecular Structure ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Tissue ◽  
Amyloid Fibrils ◽  
Β Amyloid

Features of molecule expression markers of insulin resistance in experimental Alzheimer’s disease

2015 ◽  
Vol 61 (4) ◽  
pp. 43-48
Author(s):  
Ya V Gorina ◽  
Yu K Komleva ◽  
O L Lopatina ◽  
V V Volkova ◽  
G E Gersog ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Insulin Resistance ◽  
Alzheimer's Disease ◽  
Molecular Markers ◽  
Molecular Mechanisms ◽  
Cognitive Disorders ◽  
Brain Regions ◽  
Significant Loss ◽  
Amyloid Accumulation ◽  
The Central Nervous System

Alzheimer’s Disease (AD) is characterized by a significant loss of neurons and synapses, especially in the hippocampus and cortex, the extracellular β-amyloid accumulation and formation of neurofibrillary tangles. Insulin resistance plays important role in neurodegeneration and cognitive disorders in the central nervous system, especially AD. However, the cellular and molecular mechanisms that connect insulin resistance and Alzheimer’s pathogenesis remain largely unexplained. Therefore, great importance is the identification of molecular markers that allow to define new approaches to targeted pharmacological correction of neurodegeneration. This article describes the study of the expression of molecular markers, namely, IRAP, GLUT4, and IL-18 in different brain regions (hippocampus, olfactory bulb) rats with experimental AD

Structure of β-amyloid fibrils and its relevance to their neurotoxicity: Implications for the pathogenesis of Alzheimer’s disease

2005 ◽  
Vol 99 (5) ◽  
pp. 437-447 ◽  
Author(s):  
Kazuhiro Irie ◽  
Kazuma Murakami ◽  
Yuichi Masuda ◽  
Akira Morimoto ◽  
Hajime Ohigashi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Fibrils ◽  
Β Amyloid

scholarly journals The relationship of diabetes mellitus with Alzheimer’s disease: a literature review

2021 ◽  
Author(s):  
Fábio Dias Nogueira ◽  
Ana Klara Rodrigues Alves ◽  
Barbara Beatriz Lira da Silva ◽  
Ana Kamila Rodrigues Alves ◽  
Marlilia Moura Coelho Sousa ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Insulin Resistance ◽  
Alzheimer's Disease ◽  
Glycogen Synthase ◽  
Potential Link ◽  
The Central Nervous System ◽  
Gsk 3Β ◽  
Type 3 ◽  
The Brain

Introduction: Alzheimer’s disease (AD) is closely related to diabetes mellitus (DM), and AD is also considered to be type 3 diabetes (T3D). Glycogen synthase kinase-3β (GSK-3β) may be the potential link between DM and AD. GSK-3β is one of the main factors that lead to insulin deficiency and insulin resistance, and insulin resistance is a characteristic of the development of DM. In AD, GSK-3β plays an important role in hyperphosphorylation of the tau protein (tau) associated with microtubules, which is one of the pathological features in AD. Objective: To analyze DM as a factor for the development of AD. METHODOLOGY: This is an integrative review of the literature, which is a construction of a comprehensive analysis of the literature with pre-defined steps, carried out through PubMed, 1.501 articles were found, of which 10 were selected, through the simultaneous crossing between the descriptors “Diabetes mellitus”, “Alzheimer “. Articles written in Portuguese and English published between 2016 and 2021 were inserted. Results: DM associated with insulin resistance affects psychomotor efficiency, attention, learning memory, mental flexibility, speed and executive function of the brain, thus being an independent risk factor for cognitive impairment and damage to the central nervous system, hyperglycemia, which can cause increased oxidative stress leading to progressive functional and structural abnormalities in the brain. Conclusion:The risk of dementia in patients with DM is higher than in nondiabetic patients and it is also well known that DM2 / insulin resistance is involved in AD.

β-Amyloid Peptide and Amyloid Precursor Proteins in Olfactory Mucosa of Patients with Alzheimer's Disease, Parkinson's Disease, and down Syndrome

1995 ◽  
Vol 104 (8) ◽  
pp. 655-661 ◽  
Author(s):  
Peter B. Crino ◽  
Barry Greenberg ◽  
John A. Martin ◽  
Virginia M.-Y. Lee ◽  
William D. Hill ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Down Syndrome ◽  
Amyloid Fibrils ◽  
Olfactory Mucosa ◽  
Amyloid Peptide ◽  
Β Amyloid

Dystrophic neurites are present in olfactory epithelium (OE) of patients with Alzheimer's disease (AD), Parkinson's disease (PD), and Down syndrome (DS) and occasionally in normal individuals. Cultured olfactory neuroblasts from AD patients generate carboxy terminal amyloid precursor protein (APP) fragments that contain β-amyloid (Aβ), but it is not known if deposits of Aβ and/or APP fragments occur in the OE of individuals with or without AD, PD, or DS. To determine if Aβ accumulates in the OE in situ, we probed postmortem samples of olfactory mucosa from patients with AD, PD and AD (PD/AD), and DS and AD (DS/AD), as well as from controls, using polyclonal and monoclonal antibodies to Aβ and flanking sequences in APPs. Samples of OE also were examined by thioflavin-S and electron microscopy. Labeling of Aβ was observed in 10 of 12 AD cases, 2 of 3 PD/AD cases, 3 of 4 DS/AD cases, 3 of 10 adult controls, and 4 of 6 fetal cases. The Aβ staining was seen in the basal third of the OE, in axons projecting through the lamina propria, and in metaplastic respiratory epithelium within the OE. Antibodies to other APP domains stained the OE of patients and controls. Thioflavin-S staining was present in the basal third of the OE of 8 of 9 AD patients and several PD/AD and DS/AD patients, but only in rare cells of 3 controls. Electron microscopy did not reveal amyloid fibrils in the OE. These data suggest that deposition of Aβ occurs in a variety of circumstances and is not restricted to patients with AD, PD, or DS.

scholarly journals Apomorphine Therapy for Neuronal Insulin Resistance in a Mouse Model of Alzheimer’s Disease

2017 ◽  
Vol 58 (4) ◽  
pp. 1151-1161 ◽  
Author(s):  
Norimichi Nakamura ◽  
Yasumasa Ohyagi ◽  
Tomohiro Imamura ◽  
Yuki T. Yanagihara ◽  
Kyoko M. Iinuma ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Insulin Resistance ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Model Of Alzheimer’S Disease ◽  
Neuronal Insulin Resistance

scholarly journals ADAM10 Plasma and CSF Levels Are Increased in Mild Alzheimer’s Disease

2021 ◽  
Vol 22 (5) ◽  
pp. 2416
Author(s):  
Izabela Pereira Vatanabe ◽  
Rafaela Peron ◽  
Marina Mantellatto Grigoli ◽  
Silvia Pelucchi ◽  
Giulia De Cesare ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Lower Cost ◽  
Neuroblastoma Cells ◽  
Amyloid Peptide ◽  
Membrane Lysis ◽  
The Central Nervous System ◽  
Csf Levels ◽  
Β Amyloid ◽  
Β Amyloid Peptide

ADAM10 is the main α-secretase that participates in the non-amyloidogenic cleavage of amyloid precursor protein (APP) in neurons, inhibiting the production of β-amyloid peptide (Aβ) in Alzheimer’s disease (AD). Strong recent evidence indicates the importance of the localization of ADAM10 for its activity as a protease. In this study, we investigated ADAM10 activity in plasma and CSF samples of patients with amnestic mild cognitive impairment (aMCI) and mild AD compared with cognitively healthy controls. Our results indicated that plasma levels of soluble ADAM10 were significantly increased in the mild AD group, and that in these samples the protease was inactive, as determined by activity assays. The same results were observed in CSF samples, indicating that the increased plasma ADAM10 levels reflect the levels found in the central nervous system. In SH-SY5Y neuroblastoma cells, ADAM10 achieves its major protease activity in the fraction obtained from plasma membrane lysis, where the mature form of the enzyme is detected, confirming the importance of ADAM10 localization for its activity. Taken together, our results demonstrate the potential of plasma ADAM10 to act as a biomarker for AD, highlighting its advantages as a less invasive, easier, faster, and lower-cost processing procedure, compared to existing biomarkers.

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