Protein misfolding, aggregation and mechanism of amyloid cytotoxicity: An overview and therapeutic strategies to inhibit aggregation.

Protein misfolding, aggregation and mechanism of amyloid cytotoxicity: An overview and therapeutic strategies to inhibit aggregation. Int J Biol Macromol. 2019 May 22;: Authors: Zaman M, Khan AN, Wahiduzzaman, Zakariya SM, Khan RH Abstract Protein and peptides are converted from their soluble forms into highly ordered fibrillar aggregates under various conditions inside the cell. Such transitions confer diverse neurodegenerative diseases including Alzheimer's disease, Huntington's disease Prion's disease, Parkinson's disease, polyQ and share abnormal folding of potentially cytotoxic protein species linked with degeneration and death of precise neuronal populations. Presently, major advances are made to understand and get detailed insight into the structural basis and mechanism of amyloid formation, cytotoxicity and therapeutic approaches to combat them. Here we highlight classifies and summarizes the detailed overview of protein misfolding and aggregation at their molecular level including the factors that promote protein aggregation under in vivo and in vitro conditions. In addition, we describe the recent technologies that aid the characterization of amyloid aggregates along with several models that might be responsible for amyloid induced cytotoxicity to cells. Overview on the inhibition of amyloidosis by targeting different small molecules (both natural and synthetic origin) have been also discussed, that provides important approaches to identify nov...
Source: International Journal of Biological Macromolecules - Category: Biochemistry Authors: Tags: Int J Biol Macromol Source Type: research

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Once considered a rare disease, wild type transthyretin amyloidosis (wtATTR) is currently being recognized as a prevalent disease in the elderly population, as it is estimated to be present in a significant subset of patients with heart failure with preserved ejection fraction (HFpEF) or with degenerative aortic stenosis [1,2]. The increasing population ageing, together with the availability of novel, non-invasive diagnostic tools (namely bone tracer scintigraphy), as well as the growing awareness in the medical community has led to a dramatic increase in the number of diagnosis of wtATTR in the developed countries [3].
Source: International Journal of Cardiology - Category: Cardiology Authors: Tags: Editorial Source Type: research
Resumo Prop ósito de vida (PV) é definido como o senso de que a vida tem sentido e intencionalidade, o qual desempenha papel orientador em relação às metas de vida e à tomada de decisões relativas ao uso dos recursos pessoais. Objetivos: reconhecer e analisar dados sobre PV e condições identificadas co m bom envelhecimento ou com adaptação positiva no envelhecimento. Método: foi realizada revisão integrativa de publicações de periódicos com avaliação por pares, indexadas nas bases de dados PubMed/Me...
Source: Ciencia e Saude Coletiva - Category: Occupational Health Source Type: research
Using MRI, researchers have confirmed a link between high levels of a particular...Read more on AuntMinnie.comRelated Reading: MRI reveals brain changes in technologist with COVID-19 COVID-19 neuro findings marked by mental status, stroke MRI illuminates neurologic manifestations of COVID-19 AI predicts Alzheimer's disease using MRI, patient info AI system takes human approach to brain MRI diagnosis
Source: AuntMinnie.com Headlines - Category: Radiology Source Type: news
This study aimed to characterize the neurophysiological correlates of gait in the human pedunculopontine nucleus (PPN) region and the globus pallidus internus (GPi) in Parkinson’s disease (PD) cohort. Though much is known about the PPN region through animal studies, there are limited physiological recordings from ambulatory humans. The PPN has recently garnered interest as a potential deep brain stimulation (DBS) target for improving gait and freezing of gait (FoG) in PD. We used bidirectional neurostimulators to record from the human PPN region and GPi in a small cohort of severely affected PD subjects with FoG desp...
Source: Frontiers in Human Neuroscience - Category: Neuroscience Source Type: research
Development of Specific Fluorogenic Substrates for Human β-N-Acetyl-D-hexosaminidase A for Cell-Based Assays. Chem Pharm Bull (Tokyo). 2020;68(6):526-533 Authors: Miura K, Aoyama Y, Natsu Y, Koyama R, Hirano T, Nishio T, Hakamata W Abstract Inhibitors of human β-N-acetyl-D-hexosaminidase (hHEX) A and human O-GlcNAcase (hOGA) reportedly play roles in multiple diseases, suggesting their potential for pharmacological chaperone (PC) therapy of Sandhoff disease (SD) and Tay-Sachs disease (TSD), as lysosomal storage diseases, and Alzheimer's disease and progressive supranuclear palsy, respectively...
Source: Chemical and Pharmaceutical Bulletin - Category: Drugs & Pharmacology Authors: Tags: Chem Pharm Bull (Tokyo) Source Type: research
A husband and wife team of Colombian scientists have observed Alzheimer's precursor molecules in cells taken from newborns – a boon for research into the earliest stages of a disease that doesn’t start to show symptoms until people are in their forties. #globalsouthscience
Source: Forbes.com Healthcare News - Category: Pharmaceuticals Authors: Tags: Science /science Innovation /innovation Healthcare /healthcare Editors' Pick editors-pick Source Type: news
We report a new class of natural-product-inspired covalent inhibitors of telomerase that target the catalytic active site. Age-Related Epigenetic Changes that Suppress Mitochondrial Function https://www.fightaging.org/archives/2020/03/age-related-epigenetic-changes-that-suppress-mitochondrial-function/ Today's open access research reports on two specific epigenetic changes observed in old individuals that act to reduce mitochondrial function. This joins an existing list of genes for which expression changes are known to impact mitochondrial function with age. A herd of hundreds of mitochondria are found ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
This study was carried out in accordance with the recommendations of the National Animal Care and Use Committee of the University of Buenos Aires (CICUAL). The protocol was approved by the CICUAL. Mice were kept under a 12-h light/dark cycle, with controlled temperature (23 ± 2°C) and humidity (40–60%) and had ad libitum access to food and water. To produce hTDP-43 transgenic lines, as described previously (Igaz et al., 2011), pronucleus of fertilized eggs from C57BL/6J × C3HeJ F1 matings were injected with a vector containing hTDP-43-WT cDNA. Monogenic tetO-TDP-WT12 mice wer...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
Abstract Amyloids are highly ordered beta sheet rich stable protein aggregates, which have been found to play a significant role in the onset of several degenerative diseases such as Alzheimer's disease, Huntington's disease, Parkinson's disease, Type II diabetes mellitus and so on. Aggregation of proteins leading to amyloid fibril formation via intermediate(s), is thought to be a nucleated condensation polymerization process associated with many pathological conditions. There has been extensive research to identify inhibitors of these disease oriented aggregation processes. In recent times, quantum dots, with the...
Source: Protein and Peptide Letters - Category: Biochemistry Authors: Tags: Protein Pept Lett Source Type: research
In this study, a PET camera was used to examine individual differences in the D2 system in a group consisting of 181 healthy individuals between the age of 64 and 68. All participants also had to take part in an all-inclusive performance test of the long-term episodic memory, working memory and processing speed along with an MRI assessment (which was used to measure the size of various parts of the brain). Researchers could see that the D2 system was positively linked to episodic memory, but not to working memory or to processing speed by relating PET registrations to the cognitive data. Researchers could also see that the...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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