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https://www.readbyqxmd.com/read/28294067/the-infectious-etiology-of-alzheimer-s-disease
#1
Marta Sochocka, Katarzyna Zwolińska, Jerzy Leszek
Inflammation is a part of the first line of defense of the body against invasive pathogens, and plays a crucial role in tissue regeneration and repair. A proper inflammatory response ensures the suitable resolution of inflammation and elimination of harmful stimuli, but when the inflammatory reactions are inappropriate it can lead to damage of the surrounding normal cells. The relationship between infections and Alzheimer's Disease (AD) etiology, especially late-onset AD (LOAD) has been continuously debated over the past three decades...
March 13, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28246183/bioassays-and-inactivation-of-prions
#2
Kurt Giles, Amanda L Woerman, David B Berry, Stanley B Prusiner
The experimental study of prions requires a model for their propagation. However, because prions lack nucleic acids, the simple techniques used to replicate bacteria and viruses are not applicable. For much of the history of prion research, time-consuming bioassays in animals were the only option for measuring infectivity. Although cell models and other in vitro tools for the propagation of prions have been developed, they all suffer limitations, and animal bioassays remain the gold standard for measuring infectivity...
February 28, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28208151/bacillus-calmette-gu%C3%A3-rin-confers-neuroprotection-in-a-murine-model-of-japanese-encephalitis
#3
Sahil Kulkarni, Sandeepan Mukherjee, Anupama Pandey, Ritwik Dahake, Usha Padmanabhan, Abhay S Chowdhary
OBJECTIVE: Japanese encephalitis (JE) is a debilitating disease caused by infection with the JE virus (JEV; family: Flaviviridae), which leaves neurological sequelae in survivors but more often leads to mortality. Neurodegeneration caused by inflammation is the primary pathology behind the clinical manifestation of encephalitis caused by JEV. Bacillus Calmette-Guérin (BCG) has been used in immunoprophylaxis for tuberculosis and in the adjuvant therapy of many malignancies, and has exhibited neuroprotective activities in experimental models of Parkinson and Alzheimer disease...
February 17, 2017: Neuroimmunomodulation
https://www.readbyqxmd.com/read/28049840/cytosolic-fc-receptor-trim21-inhibits-seeded-tau-aggregation
#4
William A McEwan, Benjamin Falcon, Marina Vaysburd, Dean Clift, Adrian L Oblak, Bernardino Ghetti, Michel Goedert, Leo C James
Alzheimer's disease (AD) and other neurodegenerative disorders are associated with the cytoplasmic aggregation of microtubule-associated protein tau. Recent evidence supports transcellular transfer of tau misfolding (seeding) as the mechanism of spread within an affected brain, a process reminiscent of viral infection. However, whereas microbial pathogens can be recognized as nonself by immune receptors, misfolded protein assemblies evade detection, as they are host-derived. Here, we show that when misfolded tau assemblies enter the cell, they can be detected and neutralized via a danger response mediated by tau-associated antibodies and the cytosolic Fc receptor tripartite motif protein 21 (TRIM21)...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27966067/cathepsin-b-improves-%C3%A3-amyloidosis-and-learning-and-memory-in-models-of-alzheimer-s-disease
#5
Christine M Embury, Bhagyalaxmi Dyavarshetty, Yaman Lu, Jayme L Wiederin, Pawel Ciborowski, Howard E Gendelman, Tomomi Kiyota
Amyloid-ß (Aß) precursor protein (APP) metabolism engages neuronal endolysosomal pathways for Aß processing and secretion. In Alzheimer's disease (AD), dysregulation of APP leads to excess Aß and neuronal dysfunction; suggesting that neuronal APP/Aß trafficking can be targeted for therapeutic gain. Cathepsin B (CatB) is a lysosomal cysteine protease that can lower Aß levels. However, whether CatB-modulation of Aß improves learning and memory function deficits in AD is not known. To this end, progenitor neurons were infected with recombinant adenovirus expressing CatB and recovered cell lysates subjected to proteomic analyses...
December 13, 2016: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/27882497/soluble-tlr2-and-4-concentrations-in-cerebrospinal-fluid-in-hiv-siv-related-neuropathological-conditions
#6
Khutso M Mothapo, J Ten Oever, P Koopmans, F F Stelma, S Burm, J Bajramovic, M M Verbeek, M G Olde Rikkert, M G Netea, G Koopman, A J van der Ven
HIV in the central nervous system (CNS) mainly infects microglial cells which are known to express toll-like receptors (TLRs). This paper aimed to study the role of soluble TLR2 (sTLR2), sTLR4, and other inflammatory markers in cerebrospinal fluid (CSF) in HIV/Simian immunodeficiency virus (SIV)-related neurological sequelae. We determined sTLR2 and sTLR4 levels in CSF and serum/plasma of SIV-infected rhesus macaques with and without neurological sequelae, as well as in HIV-infected patients with and without cognitive impairments and Alzheimer's disease (AD) patients and matched controls...
November 23, 2016: Journal of Neurovirology
https://www.readbyqxmd.com/read/27803664/herpes-simplex-virus-type1-hsv-1-impairs-dna-repair-in-cortical-neurons
#7
Giovanna De Chiara, Mauro Racaniello, Cristiana Mollinari, Maria Elena Marcocci, Giorgia Aversa, Alessio Cardinale, Anna Giovanetti, Enrico Garaci, Anna Teresa Palamara, Daniela Merlo
Several findings suggest that Herpes simplex virus-1 (HSV-1) infection plays a role in the neurodegenerative processes that characterize Alzheimer's disease (AD), but the underlying mechanisms have yet to be fully elucidated. Here we show that HSV-1 productive infection in cortical neurons causes the accumulation of DNA lesions that include both single (SSBs) and double strand breaks (DSBs), which are reported to be implicated in the neuronal loss observed in neurodegenerative diseases. We demonstrate that HSV-1 downregulates the expression level of Ku80, one of the main components of non-homologous end joining (NHEJ), a major pathway for the repair of DSBs...
2016: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/27733281/global-regional-and-national-life-expectancy-all-cause-mortality-and-cause-specific-mortality-for-249-causes-of-death-1980-2015-a-systematic-analysis-for-the-global-burden-of-disease-study-2015
#8
COMMENT
(no author information available yet)
BACKGROUND: Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015. These results informed an in-depth investigation of observed and expected mortality patterns based on sociodemographic measures. METHODS: We estimated all-cause mortality by age, sex, geography, and year using an improved analytical approach originally developed for GBD 2013 and GBD 2010...
October 8, 2016: Lancet
https://www.readbyqxmd.com/read/27608030/the-role-of-antimicrobial-peptides-in-influenza-virus-infection-and-their-potential-as-antiviral-and-immunomodulatory-therapy
#9
REVIEW
I-Ni Hsieh, Kevan L Hartshorn
Influenza A virus (IAV) remains a major threat that can cause severe morbidity and mortality due to rapid genomic variation. Resistance of IAVs to current anti-IAV drugs has been emerging, and antimicrobial peptides (AMPs) have been considered to be potential candidates for novel treatment against IAV infection. AMPs are endogenous proteins playing important roles in host defense through direct antimicrobial and antiviral activities and through immunomodulatory effects. In this review, we will discuss the anti-IAV and immunomodulatory effects of classical AMPs (defensins and cathelicidins), and proteins more recently discovered to have AMP-like activity (histones and Alzheimer's associated β-amyloid)...
September 6, 2016: Pharmaceuticals
https://www.readbyqxmd.com/read/27589534/elevated-epstein-barr-virus-antibody-level-is-associated-with-cognitive-decline-in-the-korean-elderly
#10
Sung-Mi Shim, Hyo-Soon Cheon, Chulman Jo, Young Ho Koh, Jihyun Song, Jae-Pil Jeon
Chronic viral infection is implicated in cognitive decline and Alzheimer's disease (AD). Our goal was to identify biomarkers for the development of amnestic mild cognitive impairment (aMCI) from cognitively normal state. To accomplish this, we analyzed plasma IgG levels against Epstein-Barr virus (EBV) and herpes simplex virus 1 (HSV-1) in study subjects with incident aMCI (Converter) and normal cognitive function (NC Control) who did or did not convert from cognitively normal state to aMCI during the 2-year follow-up period, respectively...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27567837/bacterial-infection-increases-the-risk-of-alzheimer-s-disease-an-evidence-based-assessment
#11
Priya Maheshwari, Guy D Eslick
BACKGROUND: The possibility of an infectious etiology for Alzheimer's disease (AD) has been repeatedly postulated over the past three decades, with the roles of both viruses and bacteria having been investigated. Chlamydophila (formerly Chlamydia) pneumoniae (Cpn) and spirochetal bacteria have been two of the most frequently implicated bacterial groups in AD pathogenesis. OBJECTIVE: A meta-analysis was performed where data was combined from 25 studies examining the association between AD and spirochetal bacteria or Cpn...
August 18, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27540523/the-evaluation-of-nerve-growth-factor-over-expression-on-neural-lineage-specific-genes-in-human-mesenchymal-stem-cells
#12
Yousef Mortazavi, Fatemeh Sheikhsaran, Gholamreza Khamisipour Khamisipour, Masoud Soleimani, Ali Teimuri, Somayeh Shokri
OBJECTIVE: Treatment and repair of neurodegenerative diseases such as brain tumors, spinal cord injuries, and functional disorders, including Alzheimer's disease, are challenging problems. A common treatment approach for such disorders involves the use of mesenchymal stem cells (MSCs) as an alternative cell source to replace injured cells. However, use of these cells in hosts may potentially cause adverse outcomes such as tumorigenesis and uncontrolled differentiation. In attempt to generate mesenchymal derived neural cells, we have infected MSCs with recombinant lentiviruses that expressed nerve growth factor (NGF) and assessed their neural lineage genes...
July 2016: Cell Journal
https://www.readbyqxmd.com/read/27497484/herpes-and-alzheimer-s-disease-subversion-in-the-central-nervous-system-and-how-it-might-be-halted
#13
Ruth F Itzhaki
The last 8 or so years have seen a large increase in the number of studies supporting the concept of a major role for herpes simplex virus type 1 (HSV1) in Alzheimer's disease (AD). The main advances have been made through studies in humans and in mice, investigating the likelihood of reactivation of the latent virus in brain. Others have aimed to explain the mechanisms in cells whereby the increase in amyloid-beta (Aβ) production on HSV1 infection of cells and mouse brains occurs, and the reason that infected cells make this increase...
October 18, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27489858/persistent-infections-immune-senescence-and-alzheimer-s-disease
#14
Federico Licastro, Elisa Porcellini
Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia. Classical hallmarks of AD such as amyloid deposition and neurofibrillary tangles do not completely explain AD pathogenesis. Recent investigations proposed Aβ peptide as an anti-microbial factor. Our previous works suggested that the concomitant presence of single nucleotide polymorphisms (SNPs) from AD genetic studies might impair antiviral defenses and increase the individual susceptibility to herpes virus infection...
2016: Oncoscience
https://www.readbyqxmd.com/read/27430350/electroencephalographic-markers-in-dementia
#15
REVIEW
N Malek, M R Baker, C Mann, J Greene
Dementia is a global health problem with a huge impact on the lives of those afflicted. There are several distinct diseases that are classified under the umbrella term "dementia" ranging from neurodegenerative disorders such as Alzheimer's disease to chronic infections of the central nervous system such as subacute sclerosing panencephalitis (SSPE), a rare complication of measles virus infection in childhood. Clinical features, neuropsychological profiles and imaging characteristics of the various dementia syndromes can be sufficiently distinct to distinguish them from one another...
April 2017: Acta Neurologica Scandinavica
https://www.readbyqxmd.com/read/27392871/anti-viral-properties-of-amyloid-%C3%AE-peptides
#16
Karine Bourgade, Gilles Dupuis, Eric H Frost, Tamàs Fülöp
Amyloid-β (Aβ) peptides generated by the amyloidogenic pathway of amyloid-β protein precursor processing contribute significantly to neurodegeneration characteristic of Alzheimer's disease (AD). The involvement of Aβ peptides in the etiology of AD remains a subject of debate. Data published in the last 6 years by three different groups have added a new twist by revealing that Aβ peptides could act as antimicrobial peptides (AMP) in in vitro assays against some common and clinically relevant microorganisms, inhibit replication of seasonal and pandemic strains of influenza A and, HSV-1 virus...
July 6, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27392870/herpes-simplex-virus-type-1-neuronal-infection-elicits-cellular-and-molecular-mechanisms-of-neuroinflammation-and-neurodegeneration-in-in-vitro-and-in-vivo-mice-models
#17
Carola Otth, Luis Leyton, Marukel Salamin, Francisca Acuña-Hinrichsen, Carolina Martin, Margarita I Concha
Herpes simplex virus type 1 (HSV-1) is a neurotropic virus able to establish a persistent latent infection in the host. Herpes simplex encephalitis (HSE) is associated with a high mortality rate and significant neurological, neuropsychological, and neurobehavioral sequelae, which afflict patients for life. Currently, it is unclear whether asymptomatic recurrent reactivations of HSV-1 occur in the central nervous systems in infected people, and if these events could lead to a progressive deterioration of neuronal function...
July 6, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27165780/gain-of-function-mutations-in-protein-kinase-c%C3%AE-pkc%C3%AE-may-promote-synaptic-defects-in-alzheimer-s-disease
#18
Stephanie I Alfonso, Julia A Callender, Basavaraj Hooli, Corina E Antal, Kristina Mullin, Mathew A Sherman, Sylvain E Lesné, Michael Leitges, Alexandra C Newton, Rudolph E Tanzi, Roberto Malinow
Alzheimer's disease (AD) is a progressive dementia disorder characterized by synaptic degeneration and amyloid-β (Aβ) accumulation in the brain. Through whole-genome sequencing of 1345 individuals from 410 families with late-onset AD (LOAD), we identified three highly penetrant variants in PRKCA, the gene that encodes protein kinase Cα (PKCα), in five of the families. All three variants linked with LOAD displayed increased catalytic activity relative to wild-type PKCα as assessed in live-cell imaging experiments using a genetically encoded PKC activity reporter...
May 10, 2016: Science Signaling
https://www.readbyqxmd.com/read/27110325/redox-imbalance-and-viral-infections-in-neurodegenerative-diseases
#19
REVIEW
Dolores Limongi, Sara Baldelli
Reactive oxygen species (ROS) are essential molecules for many physiological functions and act as second messengers in a large variety of tissues. An imbalance in the production and elimination of ROS is associated with human diseases including neurodegenerative disorders. In the last years the notion that neurodegenerative diseases are accompanied by chronic viral infections, which may result in an increase of neurodegenerative diseases progression, emerged. It is known in literature that enhanced viral infection risk, observed during neurodegeneration, is partly due to the increase of ROS accumulation in brain cells...
2016: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/27087243/management-of-inflammation-by-natural-polyphenols-a-comprehensive-mechanistic-update
#20
REVIEW
Souvik Sarkar, Somnath Mazumder, Shubhra J Saha, Uday Bandyopadhyay
Inflammation generates a systemic response against injury or infection from bacteria, viruses, and other pathogens. The welfare of host is the primary target of this process. However, uncontrolled or inadequate regulation of the inflammatory response produces detrimental effects leading to the generation of various chronic disorders including atherosclerosis, type-2 diabetes, neurodegenerative disease, cancer and Alzheimer's disease with severe tissue damage. The exact identity of the inflammatory stimuli is still elusive as they function in multiple pathways; therefore targeting a particular pathway does not resolve the problem...
May 27, 2016: Current Medicinal Chemistry
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