Membrane-disordering effects of β-amyloid peptides

β-Amyloid (Aβ) protein is the major constituent of senile plaques and cerebrovascular deposits characteristic of Alzheimer's disease (AD). The causal relationship between Aβ and AD-specific lesions like neurodegeneration and atrophy is still not known. The present article summarizes our studies indicating that rather low concentrations of Aβ significantly alter the fluidity of cell membranes and subcellular fractions from different tissues and different species including humans, as a possible initial step of its biological effects. Using different fluorescent probes our data show clearly that Aβ peptides specifically disturb the acylchain layer of cell membranes in a very distinct fashion. By contrast, membrane properties at the level of the polar heads of the phospholipid bilayer at the interface with membrane proteins are much less affected.

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Fibrillization of 40-residue β-Amyloid Peptides in Membrane-Like Environments Leads to Different Fibril Structures and Reduced Molecular Polymorphisms

Biomolecules ◽

10.3390/biom10060881 ◽

2020 ◽

Vol 10 (6) ◽

pp. 881

Author(s):

Qinghui Cheng ◽

Zhi-Wen Hu ◽

Yuto Tobin-Miyaji ◽

Amy E. Perkins ◽

Terrence Deak ◽

...

Keyword(s):

Human Brain ◽

Biological Membranes ◽

Structural Heterogeneity ◽

Growth Conditions ◽

Molecular Structures ◽

Phospholipid Bilayer ◽

Amyloid Peptides ◽

Amyloid Aβ ◽

Β Amyloid ◽

Aβ Fibrils

The molecular-level polymorphism in β-Amyloid (Aβ) fibrils have recently been considered as a pathologically relevant factor in Alzheimer’s disease (AD). Studies showed that the structural deviations in human-brain-seeded Aβ fibrils potentially correlated with the clinical histories of AD patients. For the 40-residue Aβ (Aβ40) fibrils derived from human brain tissues, a predominant molecular structure was proposed based on solid-state nuclear magnetic resonance (ssNMR) spectroscopy. However, previous studies have shown that the molecular structures of Aβ40 fibrils were sensitive to their growth conditions in aqueous environments. We show in this work that biological membranes and their phospholipid bilayer mimics serve as environmental factors to reduce the structural heterogeneity in Aβ40 fibrils. Fibrillization in the presence of membranes leads to fibril structures that are significantly different to the Aβ40 fibrils grown in aqueous solutions. Fibrils grown from multiple types of membranes, including the biological membranes extracted from the rats’ synaptosomes, shared similar ssNMR spectral features. Our studies emphasize the biological relevance of membranes in Aβ40 fibril structures and fibrillization processes.

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Co-localization of β-amyloid peptides, apolipoprotein E and glial markers in senile plaques in the prefrontal cortex of old rhesus monkeys

Brain Research ◽

10.1016/s0006-8993(96)01423-0 ◽

1997 ◽

Vol 751 (2) ◽

pp. 315-322 ◽

Cited By ~ 22

Author(s):

Wolfgang Härtig ◽

Gert Brückner ◽

Christina Schmidt ◽

Kurt Brauer ◽

Geert Bodewitz ◽

...

Keyword(s):

Prefrontal Cortex ◽

Apolipoprotein E ◽

Rhesus Monkeys ◽

Senile Plaques ◽

Amyloid Peptides ◽

Β Amyloid

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Magnetic Resonance Studies of β-Amyloid Peptides

Australian Journal of Chemistry ◽

10.1071/ch02268 ◽

2003 ◽

Vol 56 (5) ◽

pp. 349 ◽

Cited By ~ 13

Author(s):

Tong-Lay Lau ◽

Kevin J. Barnham ◽

Cyril C. Curtain ◽

Colin L. Masters ◽

Frances Separovic

Keyword(s):

Conformational Changes ◽

Senile Plaques ◽

Amyloid Peptide ◽

Nmr Studies ◽

Paramagnetic Resonance ◽

Amyloid Peptides ◽

Β Amyloid ◽

Β Amyloid Peptide ◽

Main Component ◽

The Relationship

The deposition of senile plaques is a characteristic event in the progression of Alzheimer's disease (AD). Associated with the progression of the disease, the main component of the deposited material, the β-amyloid peptide (Aβ), undergoes a structural transition and a toxic gain of function. For this reason, extensive structural studies of Aβ and Aβ fragments have been carried out in order to determine the relationship between neurotoxicity and conformational changes of the peptide that lead to fibril formation. NMR studies in aqueous solution and in membrane-mimicking environments are reviewed, and include the effects of temperature, pH, and metal ions on Aβ structure. In addition, electron paramagnetic resonance (EPR) studies of Aβ in model membranes and the effect of metals of Aβ are discussed and demonstrate the pleiomorphic nature of the peptide. The contradictory results obtained from the various experiments are a result of studying different fragments of Aβ and illustrate the importance of studying the full-length peptide.

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Stereoselective Determination of Amino Acids in β-Amyloid Peptides and Senile Plaques

Analytical Chemistry ◽

10.1021/ac000861q ◽

2001 ◽

Vol 73 (11) ◽

pp. 2625-2631 ◽

Cited By ~ 16

Author(s):

Gunnar Thorsén ◽

Jonas Bergquist ◽

Anita Westlind-Danielsson ◽

Björn Josefsson

Keyword(s):

Amino Acids ◽

Senile Plaques ◽

Amyloid Peptides ◽

Β Amyloid

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The Eminent Role of microRNAs in the Pathogenesis of Alzheimer's Disease

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2021.641080 ◽

2021 ◽

Vol 13 ◽

Author(s):

Mohammad Samadian ◽

Mahdi Gholipour ◽

Mohammadreza Hajiesmaeili ◽

Mohammad Taheri ◽

Soudeh Ghafouri-Fard

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Inflammatory Responses ◽

Senile Plaques ◽

Tau Proteins ◽

Aberrant Expression ◽

Amyloid Peptides ◽

Comprehensive Search ◽

Β Amyloid

Alzheimer's disease (AD) is an irrevocable neurodegenerative condition characterized by the presence of senile plaques comprising amassed β-amyloid peptides (Aβ) and neurofibrillary tangles mainly comprising extremely phosphorylated Tau proteins. Recent studies have emphasized the role of microRNAs (miRNAs) in the development of AD. A number of miRNAs, namely, miR-200a-3p, miR-195, miR-338-5p, miR-34a-5p, miR-125b-5p, miR-132, miR-384, miR-339-5p, miR-135b, miR-425-5p, and miR-339-5p, have been shown to participate in the development of AD through interacting with BACE1. Other miRNAs might affect the inflammatory responses in the course of AD. Aberrant expression of several miRNAs in the plasma samples of AD subjects has been shown to have the aptitude for differentiation of AD subjects from healthy subjects. Finally, a number of AD-modifying agents affect miRNA profile in cell cultures or animal models. We have performed a comprehensive search and summarized the obtained data about the function of miRNAs in AD in the current review article.

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Biological Signatures of Alzheimer’s Disease

Current Topics in Medicinal Chemistry ◽

10.2174/1568026620666200228095553 ◽

2020 ◽

Vol 20 (9) ◽

pp. 770-781 ◽

Cited By ~ 12

Author(s):

Poornima Sharma ◽

Anjali Sharma ◽

Faizana Fayaz ◽

Sharad Wakode ◽

Faheem H. Pottoo

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

White Matter ◽

Senile Plaque ◽

Senile Plaques ◽

Amyloid Deposition ◽

Immune Defense ◽

Amyloid Angiopathy ◽

Microvascular Changes ◽

Β Amyloid

Alzheimer’s disease (AD) is the most prevalent and severe neurodegenerative disease affecting more than 0.024 billion people globally, more common in women as compared to men. Senile plaques and amyloid deposition are among the main causes of AD. Amyloid deposition is considered as a central event which induces the link between the production of β amyloid and vascular changes. Presence of numerous biomarkers such as cerebral amyloid angiopathy, microvascular changes, senile plaques, changes in white matter, granulovascular degeneration specifies the manifestation of AD while an aggregation of tau protein is considered as a primary marker of AD. Likewise, microvascular changes, activation of microglia (immune defense system of CNS), amyloid-beta aggregation, senile plaque and many more biomarkers are nearly found in all Alzheimer’s patients. It was seen that 70% of Alzheimer’s cases occur due to genetic factors. It has been reported in various studies that apolipoprotein E(APOE) mainly APOE4 is one of the major risk factors for the later onset of AD. Several pathological changes also occur in the white matter which include dilation of the perivascular space, loss of axons, reactive astrocytosis, oligodendrocytes and failure to drain interstitial fluid. In this review, we aim to highlight the various biological signatures associated with the AD which may further help in discovering multitargeting drug therapy.

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The Influence of Ultra-Low Concentrations of Potassium Anphen on the Bioenergetic Characteristics of Mitochondria

Current Bioactive Compounds ◽

10.2174/1573407214666181116093909 ◽

2020 ◽

Vol 16 (4) ◽

pp. 537-542

Author(s):

Zhigacheva Irina ◽

Volodkin Aleksandr ◽

Rasulov Maksud

Keyword(s):

Functional State ◽

Membrane Lipids ◽

Biological Effects ◽

Dose Dependence ◽

Stress Factors ◽

Mitochondrial Membranes ◽

Oxidation Rates ◽

Pea Seedlings ◽

Low Concentrations ◽

Wide Range

Background: One of the main sources of ROS in stress conditions is the mitochondria. Excessive generation of ROS leads to oxidation of thiol groups of proteins, peroxidation of membrane lipids and swelling of the mitochondria. In this regard, there is a need to search for preparationsadaptogens that increase the body's resistance to stress factors. Perhaps, antioxidants can serve as such adaptogens. This work aims at studying the effect of antioxidant; the potassium anphen in a wide range of concentrations on the functional state of 6 day etiolated pea seedlings mitochondria (Pisum sativum L). Methods: The functional state of mitochondria was studied per rates of mitochondria respiration, by the level of lipid peroxidation and study of fatty acid composition of mitochondrial membranes by chromatography technique. Results: Potassium anphen in concentrations of 10-5 - 10-8 M and 10-13-10-16 prevented the activation of LPO in the mitochondrial membranes of pea seedlings, increased the oxidation rates of NAD-dependent substrates and succinate in the respiratory chain of mitochondria that probably pointed to the anti-stress properties of the drug. Indeed, the treatment of pea seeds with the preparation in concentrations of 10-13 M prevented the inhibition of growth of seedlings in conditions of water deficiency. Conclusion: It is assumed that the dose dependence of the biological effects of potassium anphen and the manifestation of these effects in ultra-low concentrations are due to its ability in water solutions to form a hydrate containing molecular ensembles (structures).

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