Amyloid β-Peptide Decreases Neuronal Glucose Uptake Despite Causing Increase in GLUT3 mRNA Transcription and GLUT3 Translocation to the Plasma Membrane

2002 ◽  
Vol 174 (2) ◽  
pp. 253-258 ◽  
Author(s):  
Teerasak Prapong ◽  
Janice Buss ◽  
Walter H. Hsu ◽  
Patricia Heine ◽  
Heather West Greenlee ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Glucose Uptake ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Mrna Transcription

Synaptic Silencing and Plasma Membrane Dyshomeostasis Induced by Amyloid-β Peptide are Prevented by Aristotelia chilensis Enriched Extract

2012 ◽  
Vol 31 (4) ◽  
pp. 879-889 ◽  
Author(s):  
Jorge Fuentealba ◽  
Andrea Dibarrart ◽  
Francisco Saez-Orellana ◽  
María Cecilia Fuentes-Fuentes ◽  
Carlos N. Oyanedel ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Aristotelia Chilensis

Impairment of the activity of the plasma membrane Ca2+-ATPase in Alzheimer's disease

2011 ◽  
Vol 39 (3) ◽  
pp. 819-822 ◽  
Author(s):  
Ana M. Mata ◽  
María Berrocal ◽  
M. Rosario Sepúlveda
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Plasma Membrane ◽  
Molecular Mechanisms ◽  
Neurodegenerative Disorder ◽  
Senile Plaques ◽  
Amyloid Β ◽  
Inhibitory Effect ◽  
Amyloid Β Peptide ◽  
Aβ Amyloid

AD (Alzheimer's disease) is an age-associated neurodegenerative disorder where the accumulation of neurotoxic Aβ (amyloid β-peptide) in senile plaques is a typical feature. Recent studies point out a relationship between Aβ neurotoxicity and Ca2+ dyshomoeostasis, but the molecular mechanisms involved are still under discussion. The PMCAs (plasma membrane Ca2+-ATPases) are a multi-isoform family of proteins highly expressed in brain that is implicated in the maintenance of low intraneural Ca2+ concentration. Therefore the malfunction of this pump may also be responsible for Ca2+ homoeostasis failure in AD. We have found that the Ca2+-dependence of PMCA activity is affected in human brains diagnosed with AD, being related to the enrichment of Aβ. The peptide produces an inhibitory effect on the activity of PMCA which is isoform-specific, with the greatest inhibition of PMCA4. Besides, cholesterol blocked the inhibitory effect of Aβ, which is consistent with the lack of any Aβ effect on PMCA4 found in cholesterol-enriched lipid rafts isolated from pig brain. These observations suggest that PMCAs are a functional component of the machinery that leads to Ca2+ dysregulation in AD and propose cholesterol enrichment in rafts as a protector of the Aβ-mediated inhibition on PMCA.

scholarly journals Methylene Blue Blocks and Reverses the Inhibitory Effect of Tau on PMCA Function

2019 ◽  
Vol 20 (14) ◽  
pp. 3521 ◽  
Author(s):  
Maria Berrocal ◽  
Montaña Caballero-Bermejo ◽  
Carlos Gutierrez-Merino ◽  
Ana M. Mata
Keyword(s):  
Methylene Blue ◽  
Plasma Membrane ◽  
Molecular Marker ◽  
Cell Cultures ◽  
Calcium Homeostasis ◽  
Amyloid Β ◽  
Inhibitory Effect ◽  
Therapeutic Drug ◽  
Amyloid Β Peptide ◽  
Molecular Mechanism Of Action

Methylene blue (MB) is a synthetic phenothiazine dye that, in the last years, has generated much debate about whether it could be a useful therapeutic drug for tau-related pathologies, such as Alzheimer’s disease (AD). However, the molecular mechanism of action is far from clear. Recently we reported that MB activates the plasma membrane Ca2+-ATPase (PMCA) in membranes from human and pig tissues and from cells cultures, and that it could protect against inactivation of PMCA by amyloid β-peptide (Aβ). The purpose of the present study is to further examine whether the MB could also modulate the inhibitory effect of tau, another key molecular marker of AD, on PMCA activity. By using kinetic assays in membranes from several tissues and cell cultures, we found that this phenothiazine was able to block and even to completely reverse the inhibitory effect of tau on PMCA. The results of this work point out that MB could mediate the toxic effect of tau related to the deregulation of calcium homeostasis by blocking the impairment of PMCA activity by tau. We then could conclude that MB could interfere with the toxic effects of tau by restoring the function of PMCA pump as a fine tuner of calcium homeostasis.

scholarly journals Presenilin-1 affects trafficking and processing of βAPP and is targeted in a complex with nicastrin to the plasma membrane

2002 ◽  
Vol 158 (3) ◽  
pp. 551-561 ◽  
Author(s):  
Christoph Kaether ◽  
Sven Lammich ◽  
Dieter Edbauer ◽  
Michaela Ertl ◽  
Jens Rietdorf ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Cell Surface ◽  
Secretory Pathway ◽  
Amyloid Β ◽  
Biologically Active ◽  
Dual Function ◽  
Amyloid Β Peptide ◽  
Secretase Activity ◽  
Β Amyloid ◽  
Aβ Production

Amyloid β-peptide (Aβ) is generated by the consecutive cleavages of β- and γ-secretase. The intramembraneous γ-secretase cleavage critically depends on the activity of presenilins (PS1 and PS2). Although there is evidence that PSs are aspartyl proteases with γ-secretase activity, it remains controversial whether their subcellular localization overlaps with the cellular sites of Aβ production. We now demonstrate that biologically active GFP-tagged PS1 as well as endogenous PS1 are targeted to the plasma membrane (PM) of living cells. On the way to the PM, PS1 binds to nicastrin (Nct), an essential component of the γ-secretase complex. This complex is targeted through the secretory pathway where PS1-bound Nct becomes endoglycosidase H resistant. Moreover, surface-biotinylated Nct can be coimmunoprecipitated with PS1 antibodies, demonstrating that this complex is located to cellular sites with γ-secretase activity. Inactivating PS1 or PS2 function by mutagenesis of one of the critical aspartate residues or by γ-secretase inhibitors results in delayed reinternalization of the β-amyloid precursor protein and its accumulation at the cell surface. Our data suggest that PS is targeted as a biologically active complex with Nct through the secretory pathway to the cell surface and suggest a dual function of PS in γ-secretase processing and in trafficking.

scholarly journals The plasma membrane redox system is impaired by amyloid β-peptide and in the hippocampus and cerebral cortex of 3xTgAD mice

2010 ◽  
Vol 225 (2) ◽  
pp. 423-429 ◽  
Author(s):  
Dong-Hoon Hyun ◽  
Mohamed R. Mughal ◽  
Hyunwon Yang ◽  
Ji Hyun Lee ◽  
Eun Joo Ko ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Plasma Membrane ◽  
Amyloid Β ◽  
Redox System ◽  
Amyloid Β Peptide ◽  
Plasma Membrane Redox System ◽  
Plasma Membrane Redox

Amyloid β-Peptide Inhibits Neuronal Glucose Uptake by Preventing Exocytosis

2001 ◽  
Vol 170 (2) ◽  
pp. 270-276 ◽  
Author(s):  
Etsuro Uemura ◽  
Heather West Greenlee
Keyword(s):  
Glucose Uptake ◽  
Amyloid Β ◽  
Amyloid Β Peptide

Amyloid β-peptide and Alzheimer's disease

2014 ◽  
Vol 56 ◽  
pp. 99-110 ◽  
Author(s):  
David Allsop ◽  
Jennifer Mayes
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Senile Plaques ◽  
Strong Support ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Amyloid Cascade Hypothesis ◽  
Sequence Of Events ◽  
Aβ Amyloid ◽  
Amyloid Cascade

One of the hallmarks of AD (Alzheimer's disease) is the formation of senile plaques in the brain, which contain fibrils composed of Aβ (amyloid β-peptide). According to the ‘amyloid cascade’ hypothesis, the aggregation of Aβ initiates a sequence of events leading to the formation of neurofibrillary tangles, neurodegeneration, and on to the main symptom of dementia. However, emphasis has now shifted away from fibrillar forms of Aβ and towards smaller and more soluble ‘oligomers’ as the main culprit in AD. The present chapter commences with a brief introduction to the disease and its current treatment, and then focuses on the formation of Aβ from the APP (amyloid precursor protein), the genetics of early-onset AD, which has provided strong support for the amyloid cascade hypothesis, and then on the development of new drugs aimed at reducing the load of cerebral Aβ, which is still the main hope for providing a more effective treatment for AD in the future.

Insights into amyloid disease from fly models

2014 ◽  
Vol 56 ◽  
pp. 69-83 ◽  
Author(s):  
Ko-Fan Chen ◽  
Damian C. Crowther
Keyword(s):  
Drosophila Melanogaster ◽  
Neurodegenerative Disorders ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Disease Pathogenesis ◽  
Amyloid Aggregates ◽  
Aβ Amyloid ◽  
Polypeptide Chains ◽  
Amyloid Diseases

The formation of amyloid aggregates is a feature of most, if not all, polypeptide chains. In vivo modelling of this process has been undertaken in the fruitfly Drosophila melanogaster with remarkable success. Models of both neurological and systemic amyloid diseases have been generated and have informed our understanding of disease pathogenesis in two main ways. First, the toxic amyloid species have been at least partially characterized, for example in the case of the Aβ (amyloid β-peptide) associated with Alzheimer's disease. Secondly, the genetic underpinning of model disease-linked phenotypes has been characterized for a number of neurodegenerative disorders. The current challenge is to integrate our understanding of disease-linked processes in the fly with our growing knowledge of human disease, for the benefit of patients.

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