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https://www.readbyqxmd.com/read/27882497/soluble-tlr2-and-4-concentrations-in-cerebrospinal-fluid-in-hiv-siv-related-neuropathological-conditions
#1
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
#2
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
#3
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
#4
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
#5
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 (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...
September 2, 2016: 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
#6
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
#7
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
#8
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
#9
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
#10
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...
July 18, 2016: Acta Neurologica Scandinavica
https://www.readbyqxmd.com/read/27392871/anti-viral-properties-of-amyloid-%C3%AE-peptides
#11
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
#12
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
#13
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...
2016: Science Signaling
https://www.readbyqxmd.com/read/27110325/redox-imbalance-and-viral-infections-in-neurodegenerative-diseases
#14
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
#15
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
https://www.readbyqxmd.com/read/27048338/insights-into-the-structural-features-essential-for-jak2-inhibition-and-selectivity
#16
Chao Zhao, Daulat Bikram Khadka, Won-Jea Cho
The Janus kinase 2 (JAK2)-mediated signaling pathway plays an important role in controlling cell survival, proliferation, and differentiation. A mutation of JAK2 (V617F in specific) that results in constitutive activation of the enzyme is found in patients with myeloproliferative neoplasms (MPNs), such as polycythemia vera (PV), essential thrombocythemia, and primary myelofibrosis. The genetic, biological, and physiological evidence available to date has established JAK2 inhibitors as effective chemotherapeutic agents for the treatment of MPNs as well as solid tumors, hepatitis C virus (HCV) infection, Alzheimer's disease, and Parkinson's disease...
2016: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/27046083/prion-strain-differences-in-accumulation-of-prpsc-on-neurons-and-glia-are-associated-with-similar-expression-profiles-of-neuroinflammatory-genes-comparison-of-three-prion-strains
#17
COMPARATIVE STUDY
James A Carroll, James F Striebel, Alejandra Rangel, Tyson Woods, Katie Phillips, Karin E Peterson, Brent Race, Bruce Chesebro
Misfolding and aggregation of host proteins are important features of the pathogenesis of neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, frontotemporal dementia and prion diseases. In all these diseases, the misfolded protein increases in amount by a mechanism involving seeded polymerization. In prion diseases, host prion protein is misfolded to form a pathogenic protease-resistant form, PrPSc, which accumulates in neurons, astroglia and microglia in the CNS. Here using dual-staining immunohistochemistry, we compared the cell specificity of PrPSc accumulation at early preclinical times post-infection using three mouse scrapie strains that differ in brain regional pathology...
April 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/26957302/associations-between-hepatic-functions-and-plasma-amyloid-beta-levels-implications-for-the-capacity-of-liver-in-peripheral-amyloid-beta-clearance
#18
Ye-Ran Wang, Qing-Hua Wang, Tao Zhang, Yu-Hui Liu, Xiu-Qing Yao, Fan Zeng, Jing Li, Fa-Yin Zhou, Lin Wang, Jia-Chuan Yan, Hua-Dong Zhou, Yan-Jiang Wang
Amyloid-beta (Aβ) plays a pivotal role in the pathogenesis of Alzheimer's disease (AD). Clearance of Aβ is a promising therapeutic strategy for AD. We have previously demonstrated that peripheral organs play important roles in the clearance of brain-derived Aβ. In the present study, we recruited 46 patients with liver cirrhosis and 46 normal controls and found that plasma Aβ40 and Aβ42 levels were significantly higher in the cirrhosis patients than in the normal controls. Notably, cirrhosis patients with hepatitis B virus (HBV) infection had higher plasma Aβ40 and Aβ42 levels than HBV-negative cirrhosis patients...
March 9, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/26900711/inhibition-of-chikungunya-virus-induced-cell-death-by-salicylate-derived-bryostatin-analogues-provides-additional-evidence-for-a-pkc-independent-pathway
#19
Daryl Staveness, Rana Abdelnabi, Katherine E Near, Yu Nakagawa, Johan Neyts, Leen Delang, Pieter Leyssen, Paul A Wender
Chikungunya virus (CHIKV) has been spreading rapidly, with over one million confirmed or suspected cases in the Americas since late 2013. Infection with CHIKV causes devastating arthritic and arthralgic symptoms. Currently, there is no therapy to treat this disease, and the only medications focus on relief of symptoms. Recently, protein kinase C (PKC) modulators have been reported to inhibit CHIKV-induced cell death in cell assays. The salicylate-derived bryostatin analogues described here are structurally simplified PKC modulators that are more synthetically accessible than the natural product bryostatin 1, a PKC modulator and clinical lead for the treatment of cancer, Alzheimer's disease, and HIV eradication...
April 22, 2016: Journal of Natural Products
https://www.readbyqxmd.com/read/26899580/peripheral-immune-signatures-in-alzheimer-disease
#20
David Goldeck, Jacek M Witkowski, Tamas Fülop, Graham Pawelec
According to the current paradigm, the main cause of AD is the accumulation of neurotoxic amyloid beta (Aβ) peptide aggregates resulting from the cleavage of the amyloid precursor protein into peptides of different length, with the 42 amino acid long Aβ42 being the most toxic form. Aβ can aggregate and form plaques in the brain. It further promotes the hyperphosphorylation of the tau protein which forms characteristic neurofibrillary tangles and thereby loses its important role in axonal transport and contributes to neurodegeneration...
2016: Current Alzheimer Research
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