Beta Amyloid Peptide: January 2021

Beta Amyloid Peptide: Research Paper : Effects of surface nanopatterning on internalization and amyloid aggregation of the fragment 264-277 of Nucleophosmin 1

Effects of surface nanopatterning on internalization and amyloid aggregation of the fragment 264-277 of Nucleophosmin 1

Abstract

The mechanical interpretation of the plethora of factors that governs cellular localization of amyloid aggregates is crucial for planning novel therapeutical interventions in neurodegenerative diseases since these aggregates exert a primary role in the proteostasis machinery. The uptake of Cell Penetrating Peptides (CPPs) conjugated with different amyloid polypeptides occurs via different endocytic processes regulated by cytoskeleton organization and cell morphology. Herein, we deepened the internalization of an amyloid system in cells cultured on nanopatterned surfaces that represent a powerful tool to shape cell and regulate its contractility. We analyzed the behavior of an amyloid model system, employing NPM1264-277 sequence, covalently conjugated to Tat fragment 48-60 as CPP. To investigate its internalization mechanism, we followed the formation of aggregates on two kinds of substrates: a flat and a nanopatterned surface. Herein, investigations during time were carried out by employing both confocal and second harmonic generation (SHG) microscopies. We showed that modifications of cellular environment affect peptide localization, its cytoplasmic translocation and the size of amyloid aggregates.

Keywords: Amyloid; Cell penetrating peptide; Confocal miscroscopy; Nanopatterning; Second harmonic generation.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33137636/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  



Beta Amyloid Peptide: Research Paper : Efficacy of cognitive-behavioural therapy interventions on reducing burden for caregivers of older adults with a neurocognitive disorder: a systematic review and meta-analysis

Efficacy of cognitive-behavioural therapy interventions on reducing burden for caregivers of older adults with a neurocognitive disorder: a systematic review and meta-analysis

Abstract

By 2025, 34 million people worldwide will be living with Alzheimer's disease or another form of dementia (i.e., neurocognitive disorders). Symptoms of neurocognitive disorders have functional repercussions on daily activities. People with neurocognitive disorders often rely on a caregiver to alleviate the impact of their symptoms, but this help has consequences for the caregiver. Indeed, caregivers report subjective burden, depressive symptoms, stress, anxiety and a lower quality of life than non-caregivers. Multiple cognitive-behavioral therapy (CBT) trials have been conducted to reduce these symptoms for caregivers. No meta-analysis has been conducted to evaluate the efficacy of this type of intervention on reducing subjective burden. Articles were selected from PsycNet, MEDLINE, AgeLine and ProQuest Dissertation and Theses for the period from 2000 to 2017. Article selection, data extraction and bias analysis for individual studies were completed by two independent authors who used a consensus procedure when discrepancies occurred. A total of 20 articles were included in the systematic review. Ten studies evaluated the efficacy of CBT in reducing subjective burden, and the meta-analysis suggested a significant reduction in subjective burden following CBT. Additionally, 17 studies evaluated the efficacy in reducing depressive symptoms, and the meta-analysis revealed a significant reduction for these caregivers following CBT. CBT for caregivers of individuals with a neurocognitive disorder had no impact on stress, anxiety, or quality of life.

Keywords: Caregivers; burden; cognitive-behavioral therapy intervention; dementia; mild cognitive impairment; non-pharmacological intervention; psychological symptoms; quality of life.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33125307/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  



Beta Amyloid Peptide: Research Paper : Unsaturated mannuronate oligosaccharide ameliorates β-amyloid pathology through autophagy in Alzheimer's disease cell models

Unsaturated mannuronate oligosaccharide ameliorates β-amyloid pathology through autophagy in Alzheimer's disease cell models

Abstract

Unsaturated mannuronate oligosaccharide (MOS) is an enzymatic depolymerization product from alginate-derived polymannuronate (PM). In this study, we investigated for the first time the potential therapeutic effect of MOS on Alzheimer's disease (AD) and its molecular mechanism in N2a-sw cells and 3×Tg-AD primary cortex neurons. Our results showed that MOS ranges from mannuronate dimer to mannuronate undecamer (M2-M11) with an unsaturated nonreducing terminal structure and with a double bond and 1,4-glycosidic linkages. It significantly inhibited the aggregation of amyloid-β (Aβ)1-42 oligomer, decreased expression of Aβ1-42 and reduced levels of amyloid precursor protein (APP) and BACE1. It promoted the autophagy, which involves the inactivation of mTOR signaling pathway and the facilitation of the fusion of autophagosomes and lysosomes. Finally, autophagy inhibitors blocked MOS' anti-AD actions, confirming the involvement of autophagy. In conclusion, MOS from seaweed alginate might be a promising nutraceutical or natural medicine for AD therapy.

Keywords: Alginate; Alzheimer's disease; Amyloid-β; Autophagy; Unsaturated mannuronate oligosaccharide.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33142656/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  



Beta Amyloid Peptide: Research Paper : Carbon nitride-based nanocaptor: An intelligent nanosystem with metal ions chelating effect for enhanced magnetic targeting phototherapy of Alzheimer's disease

Carbon nitride-based nanocaptor: An intelligent nanosystem with metal ions chelating effect for enhanced magnetic targeting phototherapy of Alzheimer's disease

Abstract

Metal ions imbalance, a well-established pathologic feature of alzheimer's disease (AD), ultimately results in the deposition of amyloid-β peptide (Aβ) proteins and Aβ-induced neurotoxicity. Herein, to overcome these hurdles, an intelligent Aβ nanocaptor with the capacity to chelate metal ions and targeted therapy is developed by anchoring carbon nitride (C3N4) nanodots to Fe3O4@mesoporous silica nanospheres, and decorated with benzothiazole aniline (BTA) (designated as B-FeCN). The C3N4 nanodots could effectively capture superfluous Cu2+ to suppress the formation of Cu2+-Aβ complex thereby eliminating Aβ aggregation. Simultaneously, the nanocaptor enables local low-temperature hyperthermia to promote the dissolution of preformed fiber precipitates, therefore, maximizing the therapeutic benefits. Owing to its favorable photothermal effect, the blood-brain barrier (BBB) permeability of the nanocaptor is noticeably ameliorated upon laser illumination, which conquers the limitations associated with traditional anti-AD drugs, as evidenced by in vivo and in vitro studies. Besides, leveraging on the magnetic properties of Fe3O4 core, the nanocaptor is magnetized to access to the targeted Aβ regions under extrinsic magnetic field. BTA conjugation, which specifically binds to the β2 position of the Aβ fibers, executes specific targeting at Aβ plaques, and synchronously endows the BTA-modified nanocaptor with fluorescent imaging property for sensitively detecting Aβ aggregates. In view of these superiorities, nanocaptors combine metallostasis restoration and Aβ targeted therapy can surmount the interference of copper ions, enhance BBB permeability and protect cells against Aβ-induced neurotoxicity, which provides new avenues for developing neuroprotective nanosystems for the treatment of alzheimer's disease.

Keywords: Alzheimer's disease; Aβ aggregation clearance; Blood-brain barrier; Copper ions capture; Intelligent nanocaptors; Targeted synergistic therapy.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33129186/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  



Beta Amyloid Peptide: Research Paper : Self-assembly of N-terminal Alzheimer's β-amyloid and its inhibition

Self-assembly of N-terminal Alzheimer's β-amyloid and its inhibition

Abstract

Peptide sequence modulates amyloid fibril formation and triggers Alzheimer's disease. The N-terminal region of amyloid peptide is disordered and lack any specific secondary structure. An ionic interaction of Aβ1-11 with factor XII is critical for the activation of the contact system in Alzheimer's disease. In this study, we report the self-assembly of fluctuating N-terminal Aβ1-11 into nanotubes using atomic force micrography, transmission electron microscopy, circular dichroism studies and molecular modeling studies. The effect of four polyphenols: baicalein, rutin, vanillin and cyanidin-3-O-glucoside (C3G) was also explored on the amyloid fibril inhibitor perspective using amyloid specific dye Thioflavin T (ThT). AFM micrographs suggested the self-assembly of Aβ1-11 into nanotubes after three weeks of incubation. Microwave treatment results in the conformational variation of disordered structure to β-sheet rich amyloid fibrils. The presence of salts (sodium and potassium chloride) induces the structural transformation of Aβ1-11 to super-helix. Fluorescence spectroscopy studies using ThT suggested differential inhibition of amyloid fibrils formation in the presence of polyphenols. Molecular modeling studies suggested that binding of polyphenols to Aβ1-11 through hydrophobic interaction (Phe4 and Tyr 10) and hydrogen bonding (Glu3 and Arg5) play a substantial role in stabilizing Aβ1-11-polyphenols complex. In the presence of polyphenols, Aβ1-11 transforms to hybrid nanostructures thus hindering amyloid fibril formation. These results provide structural insights and importance of the N-terminal residues in the Aβ1-42 self-assembly mechanism.

Keywords: Amyloid fibrils; Aβ(1-11); Nanotubes; Polyphenols; Self-assembly.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33143872/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  



Beta Amyloid Peptide: Research Paper : Association of PET-based stages of amyloid deposition with neuropathological markers of Aβ pathology

Association of PET-based stages of amyloid deposition with neuropathological markers of Aβ pathology

Abstract

Objective: To determine if PET-based stages of regional amyloid deposition are associated with neuropathological phases of Aβ pathology.

Methods: We applied data-driven regional frequency-based and a-priori striatum-based PET staging approaches to ante-mortem 18F-Florbetapir-PET scans of 30 cases from the Alzheimer's Disease Neuroimaging Initiative autopsy cohort, and used Bayesian regression analysis to study the associations of these in vivo amyloid stages with neuropathological Thal phases of regional Aβ plaque distribution and with semi-quantitative ratings of neocortical and striatal plaque densities.

Results: Bayesian regression revealed extreme evidence for an association of both PET-based staging approaches with Thal phases, and these associations were about 44 times more likely for frequency-based stages and 89 times more likely for striatum-based stages than for global cortical 18F-Florbetapir-PET signal. Early (i.e., neocortical-only) PET-based amyloid stages also predicted the absence of striatal/diencephalic cored plaques. Receiver operating characteristics curves revealed highly accurate discrimination between low/high Thal phases and the presence/absence of regional plaques. The median areas under the curve were 0.99 for frequency-based staging (95% credibility interval 0.97-1.00), 0.93 for striatum-based staging (0.83-1.00), and 0.87 for global 18F-Florbetapir-PET signal (0.72-0.98).

Interpretation: Our data indicate that both regional frequency- and striatum-based amyloid-PET staging approaches were superior to standard global amyloid-PET signal for differentiating between low and high degrees of regional amyloid pathology spread. Despite this, we found no evidence for the ability of either staging scheme to differentiate between low and moderate degrees of amyloid pathology which may be particularly relevant for early, preclinical stages of Alzheimer's disease.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33137247/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  



Beta Amyloid Peptide: Research Paper : Novel target for treating Alzheimer's Diseases: Crosstalk between the Nrf2 pathway and autophagy

Novel target for treating Alzheimer's Diseases: Crosstalk between the Nrf2 pathway and autophagy

Abstract

In mammals, the Keap1-Nrf2-ARE pathway (henceforth, "the Nrf2 pathway") and autophagy are major intracellular defence systems that combat oxidative damage and maintain homeostasis. p62/SQSTM1, a ubiquitin-binding autophagy receptor protein, links the Nrf2 pathway and autophagy. Phosphorylation of p62 dramatically enhances its affinity for Keap1, which induces Keap1 to release Nrf2, and the p62-Keap1 heterodimer recruits LC3 and mediates the permanent degradation of Keap1 in the selective autophagy pathway. Eventually, Nrf2 accumulates in the cytoplasm and then translocates into the nucleus to activate the transcription of downstream genes that encode antioxidant enzymes, which protect cells from oxidative damage. Since Nrf2 also upregulates the expression of the p62 gene, a p62-Keap1-Nrf2 positive feedback loop is created that further enhances the protective effect on cells. Studies have shown that the p62-activated noncanonical Nrf2 pathway is an important marker of neurodegenerative diseases. The p62-Keap1-Nrf2 positive feedback loop and the Nrf2 pathway are involved in eliminating the ROS and protein aggregates induced by AD. Therefore, maintaining the homeostasis of the p62-Keap1-Nrf2 positive feedback loop, which is a bridge between the Nrf2 pathway and autophagy, may be a potential target for the treatment of AD.

Keywords: Alzheimer's disease; Autophagy; Nrf2 pathway; Oxidative stress; p62-Keap1-Nrf2 positive feedback loop.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33144123/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  



Beta Amyloid Peptide: Research Paper : Differential compartmental processing and phosphorylation of pathogenic human tau and native mouse tau in the line 66 model of frontotemporal dementia

Differential compartmental processing and phosphorylation of pathogenic human tau and native mouse tau in the line 66 model of frontotemporal dementia

Abstract

Synapse loss is associated with motor and cognitive decline in multiple neurodegenerative disorders, and the cellular redistribution of tau is related to synaptic impairment in tauopathies, such as Alzheimer's disease and frontotemporal dementia. Here, we examined the cellular distribution of tau protein species in human tau overexpressing line 66 mice, a transgenic mouse model akin to genetic variants of frontotemporal dementia. Line 66 mice express intracellular tau aggregates in multiple brain regions and exhibit sensorimotor and motor learning deficiencies. Using a series of anti-tau antibodies, we observed, histologically, that nonphosphorylated transgenic human tau is enriched in synapses, whereas phosphorylated tau accumulates predominantly in cell bodies and axons. Subcellular fractionation confirmed that human tau is highly enriched in insoluble cytosolic and synaptosomal fractions, whereas endogenous mouse tau is virtually absent from synapses. Cytosolic tau was resistant to solubilization with urea and Triton X-100, indicating the formation of larger tau aggregates. By contrast, synaptic tau was partially soluble after Triton X-100 treatment and most likely represents aggregates of smaller size. MS corroborated that synaptosomal tau is nonphosphorylated. Tau enriched in the synapse of line 66 mice, therefore, appears to be in an oligomeric and nonphosphorylated state, and one that could have a direct impact on cognitive function.

Keywords: Tau protein; frontotemporal dementia; mass spectrometry; mouse model; protein aggregation; synaptosome; tauopathy.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33127647/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  



Beta Amyloid Peptide: Research Paper : Association of serial position scores on memory tests and hippocampal-related neuropathologic outcomes

Association of serial position scores on memory tests and hippocampal-related neuropathologic outcomes

Abstract

Objective: To determine whether serial position scores in verbal memory differentiate hippocampal-related neuropathologic outcomes, we examined these associations in a sample of older adults without dementia who underwent autopsy.

Methods: We used data from the Rush Memory and Aging Project, a longitudinal clinical-pathologic cohort study of community-dwelling adults. A total of 701 participants (mean age 82.7, 71.2% female) completed baseline cognitive evaluations and underwent brain autopsy to identify pathologic Alzheimer disease (AD), TDP-43 inclusions (defining limbic-predominant age-related TDP-43 encephalopathy [LATE]), and hippocampal sclerosis. The Consortium to Establish a Registry for Alzheimer's Disease word list memory test immediate recall trials provided serial position scores, which index the proportion of words recalled from the beginning (primacy scores) and end (recency scores) of a word list. Binary and ordinal logistic regressions examined associations between serial position scores and neuropathologic outcomes. Secondary outcomes included Alzheimer dementia and mild cognitive impairment proximate to death.

Results: Primacy and recency scores were uncorrelated (r = 0.07). Each SD of better primacy score was associated with lower likelihood of neuropathologic changes (24% lower LATE, 31% lower pathologic AD, 37% lower hippocampal sclerosis). For pathologic AD, better baseline primacy scores were associated with a 36% lower likelihood of comorbidity with LATE or hippocampal sclerosis. Primacy scores better discriminated between clinical diagnoses proximate to death, including those with mild cognitive impairment compared to no impairment. Recency scores showed weaker or no associations.

Conclusions: Primacy scores may be particularly sensitive markers of AD and related hippocampal neuropathologies. The differential predictive value of serial position scores suggests they offer complementary information about disease outcomes in addition to the routinely used total recall scores.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33144516/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  



Beta Amyloid Peptide: Research Paper : Novel deoxyvasicinone and tetrahydro-beta-carboline hybrids as inhibitors of acetylcholinesterase and amyloid beta aggregation

Novel deoxyvasicinone and tetrahydro-beta-carboline hybrids as inhibitors of acetylcholinesterase and amyloid beta aggregation

Abstract

A novel series of deoxyvasicinone-tetrahydro-beta-carboline hybrids were synthesized and evaluated as acetylcholinesterase (AChE) and β-amyloid peptide (Aβ) aggregation inhibitors for the treatment of Alzheimer's disease. The results revealed that the derivatives had multifunctional profiles, including AChE inhibition, Aβ1-42 aggregation inhibition, and neuroprotective properties. Inspiringly, hybrids 8b and 8d displayed excellent inhibitory activities against hAChE (IC50 = 0.93 and 1.08 nM, respectively) and Aβ1-42 self-aggregation (IC50 = 19.71 and 2.05 μM, respectively). In addition, 8b and 8d showed low cytotoxicity and good neuroprotective activity against Aβ1-42-induced damage in SH-SY5Y cells.

Keywords: Acetylcholinesterase; Alzheimer's disease; Deoxyvasicinone; Tetrahydro-β-carboline; β-Amyloid peptide.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33137375/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  



Beta Amyloid Peptide: Research Paper : Unraveling the NaCl Concentration Effect on the First Stages of α-Synuclein Aggregation

Unraveling the NaCl Concentration Effect on the First Stages of α-Synuclein Aggregation

Abstract

Intraneuronal aggregation of the intrinsically disordered protein α-synuclein is at the core of Parkinson's disease and related neurodegenerative disorders. Several reports show that the concentration of salts in the medium heavily affects its aggregation rate and fibril morphology, but a characterization of the individual monomeric conformations underlying these effects is still lacking. In this work, we have applied our α-synuclein-optimized coarse-grained molecular dynamics approach to decipher the structural features of the protein monomer under a range of NaCl concentrations (0.0-1.0 M). The results show that key intramolecular contacts between the terminal domains are lost at intermediate concentrations (leading to extended conformations likely to fibrillate), but recovered at high concentrations (leading to compact conformations likely to evolve toward amorphous aggregates). The pattern of direct interactions of the terminal α-synuclein domains with Na+ and Cl- ions plays a key role in explaining this effect. Our results are consistent with a recent study reporting a fibrillation enhancement at moderate NaCl concentrations but an inhibition at higher concentrations. The present work will contribute to improving our understanding of the structural features of monomeric α-synuclein, determining its NaCl-induced fibrillation propensity and the molecular basis of synucleinopathies, necessary for the future development of disease-halting therapies.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33140640/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  



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