scholarly journals Alzheimer's disease-related amyloid β peptide causes structural disordering of lipids and changes the electric properties of a floating bilayer lipid membrane

2020 ◽  
Vol 2 (8) ◽  
pp. 3467-3480 ◽  
Author(s):  
Dusan Mrdenovic ◽  
Zhangfei Su ◽  
Wlodzimierz Kutner ◽  
Jacek Lipkowski ◽  
Piotr Pieta
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Membrane ◽  
Lipid Membrane ◽  
Amyloid Β ◽  
Neuronal Cell ◽  
Bilayer Lipid Membrane ◽  
Amyloid Β Peptide ◽  
Aβ Peptide ◽  
Structural Disordering

Neurodegeneration in Alzheimer's disease is associated with disruption of the neuronal cell membrane by the amyloid β (Aβ) peptide.

Copper Modulation of Amyloid Beta 42 Interactions with Model Membranes

2012 ◽  
Vol 65 (5) ◽  
pp. 472 ◽  
Author(s):  
Daniel K. Weber ◽  
John D. Gehman ◽  
Frances Separovic ◽  
Marc-Antoine Sani
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Total Lipid ◽  
Acyl Chain ◽  
Amyloid Β ◽  
Neuronal Cell ◽  
Model Systems ◽  
Lipid Extract ◽  
Total Lipid Extract ◽  
Amyloid Β Peptide

Growing evidence supports that interactions of the amyloid-β peptide Aβ(1–42) with neuronal cell membranes and copper are involved in Alzheimer’s disease pathogenesis. We report using solid-state NMR that the peptide significantly perturbed the phosphate and upper acyl chain region of bilayers comprising brain total lipid extract to cause domain segregation. Deep headgroup perturbations were also realized for palmitoyloleoylphospatidylcholine–cholesterol model systems; however, incorporating 10 % palmitoyloleoylphosphatidylserine or the ganglioside GM1 resulted in a more peripheral interaction. Cu2+ at a 1 : 7 molar ratio to peptide caused deeper penetration into model systems, but partially attenuated interactions with brain total lipid extract. Thioflavin T assay showed that bilayers affected amyloid formation in a mode dependant on lipid content, and was further modulated by addition of Cu2+. Our data support that ternary interactions between Cu2+, lipids and Aβ(1–42) may have significance in Alzheimer’s disease, and challenge the validity of model bilayers as substitutes for natural systems.

Disease modifying strategies for the treatment of Alzheimer's disease targeted at modulating levels of the β-amyloid peptide

2005 ◽  
Vol 33 (4) ◽  
pp. 553-558 ◽  
Author(s):  
M.N. Pangalos ◽  
S.J. Jacobsen ◽  
P.H. Reinhart
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neuronal Cell Death ◽  
Amyloid Β ◽  
Neuronal Cell ◽  
Proteolytic Processing ◽  
Amyloid Peptide ◽  
Amyloid Β Peptide ◽  
Aβ Amyloid ◽  
Disease Modifying

AD (Alzheimer's disease) is characterized neuropathologically by the presence of amyloid plaques, neurofibrillary tangles and profound grey matter loss. The ‘amyloid’ hypothesis postulates that the toxic Aβ (amyloid β) peptide, enzymatically derived from the proteolytic processing of a larger protein called APP (amyloid precursor protein), is one of the principal causative factors of neuronal cell death in the brains of AD patients. As such, methods for lowering Aβ levels in the brain are of significant interest with regard to identifying novel disease modifying therapies for the treatment of AD. In this review, we will review a variety of approaches and mechanisms capable of modulating levels of Aβ.

Lipid membrane templates the ordering and induces the fibrillogenesis of Alzheimer's disease amyloid-β peptide

2008 ◽  
Vol 72 (1) ◽  
pp. 1-24 ◽  
Author(s):  
Eva Y. Chi ◽  
Canay Ege ◽  
Amy Winans ◽  
Jaroslaw Majewski ◽  
Guohui Wu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Lipid Membrane ◽  
Amyloid Β ◽  
Amyloid Β Peptide

scholarly journals The Function and Expression of ATP-Binding Cassette Transporters Proteins in the Alzheimer's Disease

2021 ◽  
Author(s):  
Asli Aykac ◽  
Ahmet Özer Sehirli
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Choroid Plexus ◽  
Abc Transporters ◽  
Amyloid Β ◽  
Neuronal Cell ◽  
Tau Proteins ◽  
Atp Binding ◽  
Aβ Peptide ◽  
Atp Binding Cassette

AbstractDespite many years of research, radical treatment of Alzheimer's disease (AD) has still not been found. Amyloid-β (Aβ) peptide is known to play an important role in the pathogenesis of this disease. AD is characterized by three main changes occurring in the central nervous system: (1) Aβ plaque accumulation that prevents synaptic communication, (2) the accumulation of hyperphosphorylated tau proteins that inhibit the transport of molecules inside neurons, and (3) neuronal cell loss of the limbic system. Mechanisms leading to Aβ accumulation in AD are excessive Aβ production as a result of mutations in amyloid precursor protein or genes, and impairment of clearance of Aβ due to changes in Aβ aggregation properties and/or Aβ removal processes. Human ATP-binding cassette (ABC) transporters are expressed in astrocyte, microglia, neuron, brain capillary endothelial cell, choroid plexus, choroid plexus epithelial cell, and ventricular ependymal cell. ABC transporters have essential detoxification and neuroprotective roles in the brain. The expression and functional changes in ABC transporters contribute to the accumulation of Aβ peptide. In conclusion, the review was aimed to summarize and highlight accumulated evidence in the literature focusing on the changing functions of human ABC transporter members, in AD pathogenesis and progression.

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.

Is it All Said for NSAIDs in Alzheimer’s Disease? Role of Mitochondrial Calcium Uptake

2018 ◽  
Vol 15 (6) ◽  
pp. 504-510 ◽  
Author(s):  
Sara Sanz-Blasco ◽  
Maria Calvo-Rodríguez ◽  
Erica Caballero ◽  
Monica Garcia-Durillo ◽  
Lucia Nunez ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Death ◽  
Amyloid Β ◽  
Epidemiological Data ◽  
Amyloid Β Peptide ◽  
Aβ Oligomers ◽  
Mitochondrial Potential ◽  
Disease Modifying Drugs ◽  
Definitive Evidence

Objectives: Epidemiological data suggest that non-steroidal anti-inflammatory drugs (NSAIDs) may protect against Alzheimer's disease (AD). Unfortunately, recent trials have failed in providing compelling evidence of neuroprotection. Discussion as to why NSAIDs effectivity is uncertain is ongoing. Possible explanations include the view that NSAIDs and other possible disease-modifying drugs should be provided before the patients develop symptoms of AD or cognitive decline. In addition, NSAID targets for neuroprotection are unclear. Both COX-dependent and independent mechanisms have been proposed, including γ-secretase that cleaves the amyloid precursor protein (APP) and yields amyloid β peptide (Aβ). Methods: We have proposed a neuroprotection mechanism for NSAIDs based on inhibition of mitochondrial Ca2+ overload. Aβ oligomers promote Ca2+ influx and mitochondrial Ca2+ overload leading to neuron cell death. Several non-specific NSAIDs including ibuprofen, sulindac, indomethacin and Rflurbiprofen depolarize mitochondria in the low µM range and prevent mitochondrial Ca2+ overload induced by Aβ oligomers and/or N-methyl-D-aspartate (NMDA). However, at larger concentrations, NSAIDs may collapse mitochondrial potential (ΔΨ) leading to cell death. Results: Accordingly, this mechanism may explain neuroprotection at low concentrations and damage at larger doses, thus providing clues on the failure of promising trials. Perhaps lower NSAID concentrations and/or alternative compounds with larger dynamic ranges should be considered for future trials to provide definitive evidence of neuroprotection against AD.

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