β-Amyloid peptides display protective activity against the human Alzheimer’s disease-associated herpes simplex virus-1

Biogerontology, Journal Year: 2014, Volume and Issue: 16(1), P. 85 - 98

Published: Nov. 7, 2014

Language: Английский

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Rapidly progressive Alzheimer’s disease features distinct structures of amyloid-β

Brain, Journal Year: 2015, Volume and Issue: 138(4), P. 1009 - 1022

Published: Feb. 13, 2015

Genetic and environmental factors that increase the risk of late-onset Alzheimer disease are now well recognized but cause variable progression rates phenotypes sporadic Alzheimer's is largely unknown. We aimed to investigate relationship between diverse structural assemblies amyloid-β clinical decline in disease. Using novel biophysical methods, we analysed levels, particle size, conformational characteristics posterior cingulate cortex, hippocampus cerebellum 48 cases with distinctly different durations, correlated data APOE gene polymorphism. In both cortex identified an extensive array distinct amyloid-β42 particles differ display N-terminal C-terminal domains, stability. contrast, amyloid-β40 present at low levels did not form a major discernible C- terminal domains were exposed. Rapidly progressive associated frequency e4 allele demonstrates considerably expanded heterogeneity amyloid-β42, higher structured composed 30-100 monomers, fewer < 30 monomers. The link rapid suggests conformers may play important role pathogenesis phenotypes. These findings indicate exhibits wide spectrum states imply existence prion-like strains.

Language: Английский

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Alzheimer's Associated β-Amyloid Protein Inhibits Influenza A Virus and Modulates Viral Interactions with Phagocytes

PLoS ONE, Journal Year: 2014, Volume and Issue: 9(7), P. e101364 - e101364

Published: July 2, 2014

Accumulation of β-Amyloid (βA) is a key pathogenetic factor in Alzheimer's disease; however, the normal function βA unknown. Recent studies have shown that can inhibit growth bacteria and fungi. In this paper we show also inhibits replication seasonal pandemic strains H3N2 H1N1 influenza A virus (IAV) vitro. The 42 amino acid fragment (βA42) had greater activity than 40 fragment. Direct incubation with βA42 was needed to achieve optimal inhibition. Using quantitative PCR assays reduce viral uptake by epithelial cells after 45 minutes supernatant at 24 hours post infection. caused aggregation IAV particles as detected light transmission electron confocal microscopy. did not stimulate neutrophil H2O2 production or extracellular trap formation on its own, but it increased both responses stimulated IAV. addition, neutrophils. reduced protein synthesis monocytes IAV-induced interleukin-6 these cells. Hence, demonstrate for first time has antiviral modulates interactions phagocytes.

Language: Английский

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Deciphering Alzheimer Disease

Cold Spring Harbor Perspectives in Medicine, Journal Year: 2011, Volume and Issue: 2(1), P. a011460 - a011460

Published: Oct. 25, 2011

Alzheimer disease represents an insidious impairment of intellect and emotional well-being. However, recent advances in biochemical pathology human genetics offer promise that effective therapeutic agents may soon be developed.

Language: Английский

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Deregulation of excitatory neurotransmission underlying synapse failure in Alzheimer's disease

Journal of Neurochemistry, Journal Year: 2013, Volume and Issue: 126(2), P. 191 - 202

Published: May 13, 2013

Abstract Alzheimer′s disease ( AD ) is the most common form of dementia in elderly. Memory loss increasingly attributed to soluble oligomers amyloid‐β peptide (AβOs), toxins that accumulate brains and target particular synapses. Glutamate receptors appear be centrally involved synaptic targeting by AβOs. Once bound neurons, AβOs dysregulate activity reduce surface expression both N ‐methyl‐ d ‐aspartate NMDA 2‐amino‐3‐(3‐hydroxy‐5‐methyl‐isoxazol‐4‐yl)propanoic acid AMPA types glutamate receptors, impairing signaling pathways plasticity. In extracellular milieu, promote accumulation excitatory amino acids, ‐serine. This leads overactivation triggering abnormal calcium signals with noxious impacts on neurons. Here, we review key findings linking deregulated neurotransmission implicating this as a primary mechanism synapse failure . We also discuss strategies counteract impact neurotransmission. particular, evidence showing inducing neuronal hyperpolarization via activation inhibitory GABA A prevents AβO‐induced excitotoxicity, suggesting could comprise possible therapeutic approach

Language: Английский

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