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https://www.readbyqxmd.com/read/28231054/alzheimer-s-disease-as-an-inflammatory-disease
#1
Marta Bolós, Juan Ramón Perea, Jesús Avila
Alzheimer's disease (AD) is a neurodegenerative condition characterized by the formation of amyloid-β plaques, aggregated and hyperphosphorylated tau protein, activated microglia and neuronal cell death, ultimately leading to progressive dementia. In this short review, we focus on neuroinflammation in AD. Specifically, we describe the participation of microglia, as well as other factors that may contribute to inflammation, in neurodegeneration.
February 23, 2017: Biomolecular Concepts
https://www.readbyqxmd.com/read/28229128/repetitive-head-impact-exposure-and-later-life-plasma-total-tau-in-former-national-football-league-players
#2
Michael L Alosco, Yorghos Tripodis, Johnny Jarnagin, Christine M Baugh, Brett Martin, Christine E Chaisson, Nate Estochen, Linan Song, Robert C Cantu, Andreas Jeromin, Robert A Stern
INTRODUCTION: Blood protein analysis of total tau (t-tau) may be a practical screening biomarker for chronic traumatic encephalopathy (CTE), a neurodegenerative tauopathy associated with repetitive head impact (RHI) exposure. We examined plasma t-tau in symptomatic former National Football League (NFL) players compared with controls and the relationship between RHI exposure and later-life plasma t-tau. METHODS: Ninety-six former NFL players (age 40-69) and 25 same-age controls underwent blood draw to determine plasma t-tau levels...
2017: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
https://www.readbyqxmd.com/read/28228716/intranasal-bmp9-ameliorates-alzheimer-disease-like-pathology-and-cognitive-deficits-in-app-ps1-transgenic-mice
#3
Zigao Wang, Lu Xiong, Wenbin Wan, Lijie Duan, Xiaojing Bai, Hengbing Zu
Alzheimer's disease (AD) is the most common type of dementia and has no effective therapies. Previous studies showed that bone morphogenetic protein 9 (BMP9), an important factor in the differentiation and phenotype maintenance of cholinergic neurons, ameliorated the cholinergic defects resulting from amyloid deposition. These findings suggest that BMP9 has potential as a therapeutic agent for AD. However, the effects of BMP9 on cognitive function in AD and its underlying mechanisms remain elusive. In the present study, BMP9 was delivered intranasally to 7-month-old APP/PS1 mice for 4 weeks...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28225806/capsaicin-reduces-alzheimer-associated-tau-changes-in-the-hippocampus-of-type-2-diabetes-rats
#4
Weijie Xu, Juanhong Liu, Delin Ma, Gang Yuan, Yan Lu, Yan Yang
Type 2 diabetes (T2D) is a high-risk factor for Alzheimer's disease (AD) due to impaired insulin signaling pathway in brain. Capsaicin is a specific transient receptor potential vanilloid 1 (TRPV1) agonist which was proved to ameliorate insulin resistance. In this study, we investigated whether dietary capsaicin could reduce the risk of AD in T2D. T2D rats were fed with capsaicin-containing high fat (HF) diet for 10 consecutive days (T2D+CAP). Pair-fed T2D rats (T2D+PF) fed with the HF-diet of average dose of T2D+CAP group were included to control for the effects of reduced food intake and body weight...
2017: PloS One
https://www.readbyqxmd.com/read/28223223/berberine-improves-cognitive-impairment-by-promoting-autophagic-clearance-and-inhibiting-production-of-%C3%AE-amyloid-in-app-tau-ps1-mouse-model-of-alzheimer-s-disease
#5
Min Huang, Xin Jiang, Yubin Liang, Qiong Liu, Siyan Chen, Yi Guo
This study investigates the neuroprotective properties of berberine (a natural isoquinoline alkaloid isolated from the Rhizoma coptidis) and finds that berberine could promote β-amyloid (Aβ) clearance and inhibit Aβ production in the triple-transgenic mouse model of Alzheimer's disease (3×Tg-AD). During the study, berberine was first administrated to treat 3×Tg-AD mice and primary neurons. Morris water maze assay, western blotting, enzyme-linked immunosorbent assay (ELISA), immunofluorescence staining and histological analysis, transmission electron microscopic analysis were then used to evaluate the effects of the berberine administration...
February 20, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28222529/progressive-motor-deficit-is-mediated-by-the-denervation-of-neuromuscular-junctions-and-axonal-degeneration-in-transgenic-mice-expressing-mutant-p301s-tau-protein
#6
Zhuoran Yin, Femke Valkenburg, Betty E Hornix, Ietje Mantingh-Otter, Xingdong Zhou, Muriel Mari, Fulvio Reggiori, Debby Van Dam, Bart J L Eggen, Peter P De Deyn, Erik Boddeke
Tauopathies include a variety of neurodegenerative diseases associated with the pathological aggregation of hyperphosphorylated tau, resulting in progressive cognitive decline and motor impairment. The underlying mechanism for motor deficits related to tauopathy is not yet fully understood. Here, we use a novel transgenic tau mouse line, Tau 58/4, with enhanced neuron-specific expression of P301S mutant tau to investigate the motor abnormalities in association with the peripheral nervous system. Using stationary beam, gait, and rotarod tests, motor deficits were found in Tau 58/4 mice already 3 months after birth, which deteriorated during aging...
February 10, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28222302/how-to-handle-adsorption-of-cerebrospinal-fluid-amyloid-%C3%AE-1-42-in-laboratory-practice-identifying-problematic-handlings-and-resolving-the-issue-by-use-of-the-a%C3%AE-42-a%C3%AE-40-ratio
#7
Eline Willemse, Kees van Uffelen, Britta Brix, Sebastiaan Engelborghs, Hugo Vanderstichele, Charlotte Teunissen
INTRODUCTION: We aimed to investigate factors defining amyloid-β (1-42) (Aβ1-42) adsorption during preanalytical workup of cerebrospinal fluid (CSF). METHODS: CSF was transferred to new tubes ≤4 times. Variables tested were different polypropylene tube brands, volumes, CSF Aβ1-42 concentrations, incubation times, pipettes, vortex intensities, and other CSF proteins, including hyperphosphorylated tau and IL-1RAcP. An enquiry assessed the number of transfers in current practice...
February 18, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28222213/rab7a-regulates-tau-secretion
#8
Lilia Rodriguez, Nguyen-Vi Mohamed, Alexandre Desjardins, Roger Lippé, Edward Fon, Nicole Leclerc
The axonal microtubule-associated protein TAU, involved in Alzheimer's disease (AD), can be found in the extracellular space where it could be taken up by neurons, an event that is believed to contribute to the propagation of tau pathology in the brain. Since the small GTPase Rab7A is involved in the trafficking of endosomes, autophagosomes and lysosomes, and RAB7A gene expression and protein levels are upregulated in AD patients, we tested the hypothesis that Rab7A was involved in Tau secretion. We previously reported that both primary cortical neurons and HeLa cells overexpressing human TAU can release Tau...
February 21, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28222093/active-zone-proteins-are-transported-via-distinct-mechanisms-regulated-by-par-1-kinase
#9
Kara R Barber, Julia Tanquary, Keegan Bush, Amanda Shaw, Michael Woodson, Michael Sherman, Yogesh P Wairkar
Disruption of synapses underlies a plethora of neurodevelopmental and neurodegenerative disease. Presynaptic specialization called the active zone plays a critical role in the communication with postsynaptic neuron. While the role of many proteins at the active zones in synaptic communication is relatively well studied, very little is known about how these proteins are transported to the synapses. For example, are there distinct mechanisms for the transport of active zone components or are they all transported in the same transport vesicle? Is active zone protein transport regulated? In this report we show that overexpression of Par-1/MARK kinase, a protein whose misregulation has been implicated in Autism spectrum disorders (ASDs) and neurodegenerative disorders, lead to a specific block in the transport of an active zone protein component- Bruchpilot at Drosophila neuromuscular junctions...
February 21, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28219659/dementia-like-pathology-in-type-2-diabetes-a-novel-microrna-mechanism
#10
Anuradha Kalani, Pankaj Chaturvedi, Claudio Maldonado, Philip Bauer, Irving G Joshua, Suresh C Tyagi, Neetu Tyagi
Although type-2 diabetes (T2D) has been reported to increase the risk of cognitive dysfunction and dementia, the underlying mechanisms remain unclear. Dementia-like pathology is attributed to the accumulation of cellular prion protein (PrP(c)) which plays a role in cognitive dysfunction. However, its involvement and regulation in diabetic dementia-like pathology is not well understood. Using T2D db/db (leptin receptor knockout) mice subjected to object recognition and Y-maze behavioral tests, we determined that short-term memory was compromised and that the mice displayed abrupt spontaneous behaviour compared to db/m control mice...
February 17, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28219319/biomarkers-in-alzheimer-s-disease-recent-update
#11
Sushil Sharma, Walter Lipincott
Alzheimer disease (AD) is an age-related neurodegenerative disorder, characterized by loss of memory and cognitive function. It is the common cause of dementia in elderly and is a global health concern as the population of people aged 85 and older, is growing alarmingly. Although pharmacotherapy for the treatment of AD has improved, lot of work remains to treat this devastating disease. AD pathology begins even before the onset of clinical symptoms. Because therapies could be more effective if implemented early in the disease progression, it is highly prudent to discover reliable biomarkers, to detect its exact pathophysiology during pre-symptomatic stage...
February 20, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28218978/biochemical-characterization-of-metabolism-based-atrazine-resistance-in-amaranthus-tuberculatus-and-identification-of-an-expressed-gst-associated-with-resistance
#12
Anton F Evans, Sarah R O'Brien, Rong Ma, Aaron G Hager, Chance W Riggins, Kris N Lambert, Dean E Riechers
Rapid detoxification of atrazine in naturally tolerant crops such as maize (Zea mays) and grain sorghum (Sorghum bicolor) results from glutathione S-transferase (GST) activity. In previous research, two atrazine-resistant waterhemp (Amaranthus tuberculatus) populations from Illinois, U.S.A. (designated ACR and MCR) displayed rapid formation of atrazine-glutathione (GSH) conjugates, implicating elevated rates of metabolism as the resistance mechanism. Our main objective was to utilize protein purification combined with qualitative proteomics to investigate the hypothesis that enhanced atrazine detoxification, catalyzed by distinct GSTs, confers resistance in ACR and MCR...
February 20, 2017: Plant Biotechnology Journal
https://www.readbyqxmd.com/read/28218850/impact-of-phosphorylation-and-pseudo-phosphorylation-on-the-early-stages-of-aggregation-of-the-microtubule-associated-protein-tau
#13
Dmitriy V Prokopovich, John W Whittaker, Micaiah M Muthee, Azka Ahmed, Luca Larini
The microtubule associated protein tau regulates the stability of microtubules within neurons in the central nervous system. In turn, microtubules are responsible for the remodeling of the cytoskeleton that ultimately leads to the formation or pruning of new connections among neurons. As a consequence, dysfunction of tau is associated with many forms of dementia as well as Alzheimer's disease. In the brain, tau activity is regulated by its phosphorylation state. Phosphorylation is a post-translational modification of proteins that adds a phosphate group to the side chain of an amino acid...
February 20, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28218749/mechanistic-basis-for-the-recognition-of-a-misfolded-protein-by-the-molecular-chaperone-hsp90
#14
Javier Oroz, Jin Hae Kim, Bliss J Chang, Markus Zweckstetter
The critical toxic species in over 40 human diseases are misfolded proteins. Their interaction with molecular chaperones such as Hsp90, which preferentially interacts with metastable proteins, is essential for the blocking of disease progression. Here we used nuclear magnetic resonance (NMR) spectroscopy to determine the three-dimensional structure of the misfolded cytotoxic monomer of the amyloidogenic human protein transthyretin, which is characterized by the release of the C-terminal β-strand and perturbations of the A-B loop...
February 20, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28218731/a-single-use-in-vitro-biosensor-for-the-detection-of-t-tau-protein-a-biomarker-of-neuro-degenerative-disorders-in-pbs-and-human-serum-using-differential-pulse-voltammetry-dpv
#15
Yifan Dai, Alireza Molazemhosseini, Chung Chiun Liu
A single-use, in vitro biosensor for the detection of T-Tau protein in phosphate-buffer saline (PBS) and undiluted human serum was designed, manufactured, and tested. Differential pulse voltammetry (DPV) served as the transduction mechanism. This biosensor consisted of three electrodes: working, counter, and reference electrodes fabricated on a PET sheet. Both working and counter electrodes were thin gold film, 10 nm in thickness. Laser ablation technique was used to define the size and structure of the biosensor...
February 19, 2017: Biosensors
https://www.readbyqxmd.com/read/28215745/astrocyte-transport-of-glutamate-and-neuronal-activity-reciprocally-modulate-tau-pathology-in-drosophila
#16
Jason G Kilian, Heng-Wei Hsu, Kenneth Mata, Fred W Wolf, Masashi Kitazawa
Abnormal buildup of the microtubule associated protein tau is a major pathological hallmark of SAlzheimer's disease (AD)and various tauopathies. The mechanisms by which pathological tau accumulates and spreads throughout the brain remain largely unknown. Previously, we demonstrated that a restoration of the major astrocytic glutamate transporter, GLT1, ameliorated a buildup of tau pathology and rescued cognition in a mouse model of AD. We hypothesized thataberrant extracellular glutamate and abnormal neuronal excitatory activities promoted tau pathology...
February 16, 2017: Neuroscience
https://www.readbyqxmd.com/read/28213439/tau-and-%C3%AE-amyloid-are-associated-with-medial-temporal-lobe-structure-function-and-memory-encoding-in-normal-aging
#17
Shawn M Marks, Samuel N Lockhart, Suzanne L Baker, William J Jagust
Normal aging is associated with decline in episodic memory, and also with aggregation of the β-amyloid (Aβ) and tau proteins and atrophy of medial temporal lobe structures crucial to memory formation. While some evidence suggests that Aβ is associated with aberrant neural activity, the relationships between these two aggregated proteins, neural function, and brain structure are poorly understood. Using in vivo human Aβ and tau imaging, we demonstrate that increased Aβ and tau are both associated with aberrant functional magnetic resonance imaging activity in the medial temporal lobes during memory encoding in cognitively normal older adults...
February 17, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28212403/cerebrospinal-fluid-biomarkers-of-infantile-congenital-hydrocephalus
#18
David D Limbrick, Brandon Baksh, Clinton D Morgan, Gakwaya Habiyaremye, James P McAllister, Terrie E Inder, Deanna Mercer, David M Holtzman, Jennifer Strahle, Michael J Wallendorf, Diego M Morales
INTRODUCTION: Hydrocephalus is a complex neurological disorder with a pervasive impact on the central nervous system. Previous work has demonstrated derangements in the biochemical profile of cerebrospinal fluid (CSF) in hydrocephalus, particularly in infants and children, in whom neurodevelopment is progressing in parallel with concomitant neurological injury. The objective of this study was to examine the CSF of children with congenital hydrocephalus (CHC) to gain insight into the pathophysiology of hydrocephalus and identify candidate biomarkers of CHC with potential diagnostic and therapeutic value...
2017: PloS One
https://www.readbyqxmd.com/read/28209268/inorganic-mercury-prevents-the-differentiation-of-sh-sy5y-cells-amyloid-precursor-protein-microtubule-associated-proteins-and-ros-as-potential-targets
#19
Miguel Chin Chan, Elizabeth Bautista, Isabel Alvarado-Cruz, Betzabet Quintanilla-Vega, José Segovia
Exposure to mercury (Hg) occurs through different pathways and forms including methylmecury (MeHg) from seafood and rice, ethylmercury (EtHg), and elemental Hg (Hg(0)) from dental amalgams and artisanal gold mining. Once in the brain all these forms are transformed to inorganic Hg (I-Hg), where it bioaccumulates and remains for long periods. Hg is a well-known neurotoxicant, with its most damaging effects reported during brain development, when cellular key events, such as cell differentiation take place. A considerable number of studies report an impairment of neuronal differentiation due to MeHg exposure, however the effects of I-Hg, an important form of Hg found in brain, have received less attention...
February 6, 2017: Journal of Trace Elements in Medicine and Biology
https://www.readbyqxmd.com/read/28208320/dynamic-model-for-kinesin-mediated-long-range-transport-and-its-local-traffic-jam-caused-by-tau-proteins
#20
Woochul Nam, Bogdan I Epureanu
In neurons, several intracellular cargoes are transported by motor proteins (kinesins) which walk on microtubules (MTs). However, kinesins can possibly unbind from the MTs before they reach their destinations. The unbound kinesins randomly diffuse in neurons until they bind to MTs. Then, they walk again along the MTs to continue their tasks. Kinesins repeat this cycle of motion until they transport their cargoes to the destinations. However, most previous models mainly focused on the motion of kinesins when they walk on MTs...
January 2017: Physical Review. E
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