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alzheimer's disease prion diseases

Heidrun Maja Ries, Carmen Nussbaum-Krammer
A particular subgroup of protein-misfolding diseases, comprising Alzheimer's and Parkinson's disease, involves amyloidogenic proteins that can form alternative pathogenic conformations with a high tendency to self-assemble into oligomeric and fibrillar species. Although misfolded proteins have been clearly linked to disease, the exact nature of the toxic species remains highly controversial. Increasing evidence suggests that there is little correlation between the occurrence of macroscopic protein deposits and toxic phenotypes in affected cells and tissues...
October 15, 2016: Essays in Biochemistry
Matthias Schmitz, Maria Cramm, Franc Llorens, Dominik Müller-Cramm, Steven Collins, Ryuichiro Atarashi, Katsuya Satoh, Christina D Orrù, Bradley R Groveman, Saima Zafar, Walter J Schulz-Schaeffer, Byron Caughey, Inga Zerr
The development and adaption of in vitro misfolded protein amplification systems has been a major innovation in the detection of abnormally folded prion protein scrapie (PrP(Sc)) in human brain and cerebrospinal fluid (CSF) samples. Herein, we describe a fast and efficient protein amplification technique, real-time quaking-induced conversion (RT-QuIC), for the detection of a PrP(Sc) seed in human brain and CSF. In contrast to other in vitro misfolded protein amplification assays-such as protein misfolding cyclic amplification (PMCA)-which are based on sonication, the RT-QuIC technique is based on prion seed-induced misfolding and aggregation of recombinant prion protein substrate, accelerated by alternating cycles of shaking and rest in fluorescence plate readers...
November 2016: Nature Protocols
Lisa Gasperini, Elisa Meneghetti, Giuseppe Legname, Federico Benetti
Essential elements as copper and iron modulate a wide range of physiological functions. Their metabolism is strictly regulated by cellular pathways, since dysregulation of metal homeostasis is responsible for many detrimental effects. Neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and prion diseases are characterized by alterations of metal ions. These neurodegenerative maladies involve proteins that bind metals and mediate their metabolism through not well-defined mechanisms. Prion protein, for instance, interacts with divalent cations via multiple metal-binding sites and it modulates several metal-dependent physiological functions, such as S-nitrosylation of NMDA receptors...
2016: Frontiers in Neuroscience
Agata Mata, Laura Urrea, Silvia Vilches, Franc Llorens, Katrin Thüne, Juan-Carlos Espinosa, Olivier Andréoletti, Alejandro M Sevillano, Juan María Torres, Jesús Rodríguez Requena, Inga Zerr, Isidro Ferrer, Rosalina Gavín, José Antonio Del Río
Reelin is an extracellular glycoprotein involved in key cellular processes in developing and adult nervous system, including regulation of neuronal migration, synapse formation, and plasticity. Most of these roles are mediated by the intracellular phosphorylation of disabled-1 (Dab1), an intracellular adaptor molecule, in turn mediated by binding Reelin to its receptors. Altered expression and glycosylation patterns of Reelin in cerebrospinal and cortical extracts have been reported in Alzheimer's disease...
October 10, 2016: Molecular Neurobiology
Vishwanath Sivalingam, Nalla Lakshmi Prasanna, Neetu Sharma, Archana Prasad, Basant K Patel
Misfolded β-sheet-rich protein aggregates termed amyloid, deposit in vivo leading to debilitating diseases such as Alzheimer's, prion and renal amyloidosis diseases etc. Strikingly, amyloid can induce conversion of their natively folded monomers into similarly aggregated conformation via 'seeding'. The specificity of seeding is well documented in vivo for prions, where prion-variants arising from conformationally altered amyloids of the same protein, faithfully seed monomers into amyloid displaying the original variant's conformation...
September 28, 2016: Biophysical Chemistry
Shambhunath Bose, Jungsook Cho
Protein misfolding, which is known to cause several serious diseases, is an emerging field that addresses multiple therapeutic areas. Misfolding of a disease-specific protein in the central nervous system ultimately results in the formation of toxic aggregates that may accumulate in the brain, leading to neuronal cell death and dysfunction, and associated clinical manifestations. A large number of neurodegenerative diseases in humans, including Alzheimer's, Parkinson's, Huntington's, and prion diseases, are primarily caused by protein misfolding and aggregation...
October 1, 2016: Ageing Research Reviews
Cornelia M Wilson, Gohar Mushtaq, Mohammad A Kamal, Faraj Terro
Endoproteolysis is a normal post-translational process in the eukaryotic cell that plays played a role early on in protein evolution allowing protein catabolism and the generation of amino acids. Endoproteolytic cleavage regulates many crucial cellular processes including the activity of many proteins, their protein-protein interactions and the amplification of cell signals. Not surprisingly, disruption or alternation of endoproteolytic cleavage may be the root cause of many human diseases such as Alzheimer's disease, Huntington's disease and prion diseases...
September 22, 2016: CNS & Neurological Disorders Drug Targets
William A Banks, Andrej Kovac, Petra Majerova, Kristin M Bullock, Min Shi, Jing Zhang
Tauopathies are a hallmark of many neurodegenerative diseases, including Alzheimer's disease and traumatic brain injuries. It has been demonstrated that amyloid-beta peptides, alpha-synuclein, and prion proteins cross the blood-brain barrier (BBB), contributing to their abilities to induce disease. Very little is known about whether tau proteins can cross the BBB. Here we systematically characterized several key forms of tau proteins to cross the BBB, including Tau-441 (2N4R), Tau-410 (2N3R), truncated tau 151-391 (0N4R), and truncated tau 121-227...
September 20, 2016: Journal of Alzheimer's Disease: JAD
Camelia Quek, Andrew F Hill
Extracellular vesicles, including exosomes, are small membranous vesicles released from many biotypes, contributing to the disease progression and spreading. These extracellular vesicles provide an important mode of cell-to-cell communication by delivering proteins, lipids and RNA to target cells. Exosomes are found associated with neurodegenerative diseases, which are characterised by progressive degeneration of neurons and often associated with misfolded protein. The common diseases include Parkinson's disease (PD), Alzheimer's diseases (AD), amyotrophic lateral sclerosis (ALS), and the prion diseases...
September 19, 2016: Biochemical and Biophysical Research Communications
Gabor G Kovacs
Recent studies on iatrogenic Creutzfeldt-Jakob disease (CJD) raised concerns that one of the hallmark lesions of Alzheimer disease (AD), amyloid-β (Aβ), may be transmitted from human-to-human. The neuropathology of AD-related lesions is complex. Therefore, many aspects need to be considered in deciding on this issue. Observations of recent studies can be summarized as follows: 1) The frequency of iatrogenic CJD cases with parencyhmal and vascular Aβ deposits is statistically higher than expected; 2) The morphology and distribution of Aβ deposition may show distinct features; 3) The pituitary and the dura mater themselves may serve as potential sources of Aβ seeds; 4) Cadaveric dura mater from two examined cases shows Aβ deposition; and 5) There is a lack of evidence that the clinical phenotype of AD appears following the application of cadaveric pituitary hormone or dura mater transplantation...
September 20, 2016: Prion
Edward Málaga-Trillo, Katharina Ochs
Prions and Amyloid beta (Aβ) peptides induce synaptic damage via complex mechanisms that include the pathological alteration of intracellular signaling cascades. The host-encoded cellular prion protein (PrP(C)) acts as a high-affinity cell surface receptor for both toxic species and it can modulate the endocytic trafficking of the N-methyl D-aspartate (NMDA) receptor and E-cadherin adhesive complexes via Src family kinases (SFKs). Interestingly, SFK-mediated control of endocytosis is a widespread mechanism used to regulate the activity of important transmembrane proteins, including neuroreceptors for major excitatory and inhibitory neurotransmitters...
September 20, 2016: Prion
Santiago V Salazar, Stephen M Strittmatter
Soluble oligomers of amyloid-beta (Aβo) are implicated by biochemical and genetic evidence as a trigger for Alzheimer's disease (AD) pathophysiology. A key step is Aβo interaction with the neuronal surface to initiate a cascade of altered signal transduction leading to synaptic dysfunction and damage. This review discusses neuronal cell surface molecules with high affinity selectively for oligomeric disease-associated states of Aβ, with a particular focus on the role of cellular prion protein (PrP(C)) in this process...
September 14, 2016: Biochemical and Biophysical Research Communications
Parijat Kabiraj, Jose Eduardo Marin, Armando Varela-Ramirez, Mahesh Narayan
Amyloid beta (Aβ) aggregation is generally associated with Alzheimer's onset. Here, we demonstrate that incubation of dopaminergic SH-SY5Y cells with an Aβ peptide fragment (an 11-mer composed of residues 25-35; Aβ (25-35)) results in elevated intracellular nitrosative stress and induces chemical mutation of protein disulfide isomerase (PDI), an endoplasmic reticulum-resident oxidoreductase chaperone. Furthermore, Aβ (25-35) provokes aggregation of both the minor and major biomarkers of Parkinson's disease, namely, synphilin-1 and α-synuclein, respectively...
October 3, 2016: ACS Chemical Neuroscience
Edel Hennessy, Shane Gormley, Ana Belen Lopez-Rodriguez, Caoimhe Murray, Carol Murray, Colm Cunningham
Inflammation influences chronic neurodegeneration but its precise roles are not yet clear. Systemic inflammation caused by infection, trauma or co-morbidity can alter the brain's inflammatory status, produce acute cognitive impairments, such as delirium, and drive new pathology and accelerated decline. Consistent with this, elevated systemic TNF-α is associated with more rapid cognitive decline over 6 months in Alzheimer's disease patients. In the current study we challenged normal animals and those with existing progressive neurodegeneration (ME7 prion disease) with TNF-α (i...
September 12, 2016: Brain, Behavior, and Immunity
Lígia Pimentel, Ana Gomes, Manuela Pintado, Luis Miguel Rodríguez-Alcalá
The lipid fraction of milk is one of the most complex matrixes in foodstuffs due to the presence of a high number of moieties with different physical and chemical properties. Glycerolipids include glycerol and two fatty acids esterified in positions sn-1 and sn-2 with higher concentration of unsaturated fatty acids than in the triglyceride fraction of milk. Sphingolipids consist of a sphingoid base linked to a fatty acid across an amide bond. Their amphiphilic nature makes them suitable to be added into a variety of foods and recent investigations show that phospholipids, mainly phosphatidylserine and sphingomyelin, can exert antimicrobial, antiviral, and anticancer activities as well as positive effects in Alzheimer's disease, stress, and memory decline...
2016: Journal of Analytical Methods in Chemistry
Roger A Moore, Young Pyo Choi, Mark W Head, James W Ironside, Robert Faris, Diane L Ritchie, Gianluigi Zanusso, Suzette Alise Priola
Aggregated and protease-resistant mammalian prion protein (PrPSc) is the primary protein component of infectious prions. Enriched PrPSc preparations are often used to study the mechanisms underlying prion disease. However, most enrichment procedures are relatively non-specific and tend to yield significant amounts of non-PrPSc components, including various proteins that could confound functional and structural studies. It is thus important to identify these proteins and assess their potential relevance to prion pathogenesis...
September 5, 2016: Journal of Proteome Research
Hasier Eraña, Vanesa Venegas, Jorge Moreno, Joaquín Castilla
Prion diseases or Transmissible Spongiform Encephalopathies (TSEs) are a group of fatal neurodegenerative disorders affecting several mammalian species. Its causative agent, disease-associated prion protein (PrP(d)), is a self-propagating β-sheet rich aberrant conformation of the cellular prion protein (PrP(C)) with neurotoxic and aggregation-prone properties, capable of inducing misfolding of PrP(C) molecules. PrP(d) is the major constituent of prions and, most importantly, is the first known example of a protein with infectious attributes...
August 30, 2016: Biochemical and Biophysical Research Communications
Heiko Braak, Kelly Del Tredici
Experimental data indicate that transneuronal propagation of abnormal protein aggregates in neurodegenerative proteinopathies, such as sporadic Alzheimer's disease (AD) and Parkinson's disease (PD), is capable of a self-propagating process that leads to a progression of neurodegeneration and accumulation of prion-like particles. The mechanisms by which misfolded tau and α-synuclein possibly spread from one involved nerve cell to the next in the neuronal chain to induce abnormal aggregation are still unknown...
August 31, 2016: Cold Spring Harbor Perspectives in Biology
Tatiana Melnikova, DaMin Park, Lauren Becker, Deidre Lee, Eugenia Cho, Nuzhat Sayyida, Jing Tian, Karen Bandeen-Roche, David R Borchelt, Alena V Savonenko
Sex differences are a well-known phenomenon in Alzheimer's disease (AD), with women having a higher risk for AD than men. Many AD mouse models display a similar sex-dependent pattern, with females showing earlier cognitive deficits and more severe neuropathology than males. However, whether those differences are relevant to human disease is unclear. Here we show that in AD mouse models that overexpress amyloid precursor protein (APP) under control of the prion protein promoter (PrP), female transgenic mice have higher APP expression than males, complicating interpretations of the role of sex-related factors in such models...
August 26, 2016: Neurobiology of Disease
Lilian Calderón-Garcidueñas, José Avila-Ramírez, Ana Calderón-Garcidueñas, Tonatiuh González-Heredia, Hilda Acuña-Ayala, Chih-Kai Chao, Charles Thompson, Rubén Ruiz-Ramos, Victor Cortés-González, Luz Martínez-Martínez, Mario Alberto García-Pérez, Jacques Reis, Partha S Mukherjee, Ricardo Torres-Jardón, Ingolf Lachmann
Exposure to fine particulate matter (PM2.5) and ozone (O3) above US EPA standards is associated with Alzheimer's disease (AD) risk, while Mn toxicity induces parkinsonism. Mexico City Metropolitan Area (MCMA) children have pre- and postnatal sustained and high exposures to PM2.5, O3, polycyclic aromatic hydrocarbons, and metals. Young MCMA residents exhibit frontal tau hyperphosphorylation and amyloid-β (Aβ)1 - 42 diffuse plaques, and aggregated and hyperphosphorylated α-synuclein in olfactory nerves and key brainstem nuclei...
September 6, 2016: Journal of Alzheimer's Disease: JAD
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