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https://www.readbyqxmd.com/read/28922400/protein-folding-misfolding-and-aggregation-the-importance-of-two-electron-stabilizing-interactions
#1
Andrzej Stanisław Cieplak
Proteins associated with neurodegenerative diseases are highly pleiomorphic and may adopt an all-α-helical fold in one environment, assemble into all-β-sheet or collapse into a coil in another, and rapidly polymerize in yet another one via divergent aggregation pathways that yield broad diversity of aggregates' morphology. A thorough understanding of this behaviour may be necessary to develop a treatment for Alzheimer's and related disorders. Unfortunately, our present comprehension of folding and misfolding is limited for want of a physicochemical theory of protein secondary and tertiary structure...
2017: PloS One
https://www.readbyqxmd.com/read/28922155/phospho-tau-accumulation-and-structural-alterations-of-the-golgi-apparatus-of-cortical-pyramidal-neurons-in-the-p301s%C3%A2-tauopathy-mouse-model
#2
Alejandro Antón-Fernández, Jesús Merchán-Rubira, Jesús Avila, Félix Hernández, Javier DeFelipe, Alberto Muñoz
The Golgi apparatus (GA) is a highly dynamic organelle involved in the processing and sorting of cellular proteins. In Alzheimer's disease (AD), it has been shown to decrease in size and become fragmented in neocortical and hippocampal neuronal subpopulations. This fragmentation and decrease in size of the GA in AD has been related to the accumulation of hyperphosphorylated tau. However, the involvement of other pathological factors associated with the course of the disease, such as the extracellular accumulation of amyloid-β (Aβ) aggregates, cannot be ruled out, since both pathologies are present in AD patients...
September 8, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28921979/design-syntheses-and-in-vitro-evaluation-of-new-fluorine-18-radiolabeled-tau-labeling-molecular-probes
#3
Luka Rejc, Lojze Šmid, Vladimir Kepe, Črtomir Podlipnik, Amalija Golobič, Mara Bresjanac, Jorge R Barrio, Andrej Petrič, Janez Košmrlj
Deposition of aggregates of hyperphosphorylated tau protein is a hallmark of tauopathies like Alzheimer and many other neurodegenerative diseases. A sensitive and selective method of in vivo detection of tau-aggregate presence and distribution could provide the means of an early diagnosis of tau-associated diseases. Furthermore, the use of selective molecular probes that enable histochemical differentiation of protein aggregates post mortem would be advantageous for the insight into the properties of tau protein aggregates...
September 18, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28920532/the-impact-of-traumatic-brain-injury-on-later-life-effects-on-normal-aging-and-neurodegenerative-diseases
#4
Grace Sophia Griesbach, Brent E Masel, Richard Edward Helvie, Mark Ashley
The acute and chronic effects of traumatic brain injury (TBI) have been widely described; however, there is limited knowledge on how a TBI sustained during early or mid adulthood will influence aging. Epidemiological studies have explored whether TBI poses a risk for dementia and other neurodegenerative diseases associated with aging. We will discuss the influence of TBI and resulting medical comorbidities such as endocrine, sleep and inflammatory disturbances on age-related grey and white matter changes and cognitive decline...
September 16, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/28919235/alzheimer-s-disease-like-paired-helical-filament-assembly-from-truncated-tau-protein-is-independent-of-disulphide-cross-linking
#5
Youssra K Al-Hilaly, Saskia J Pollack, Devkee Vadukul, Francesca Citossi, Janet E Rickard, Michael Simpson, John M D Storey, Charles R Harrington, Claude M Wischik, Louise C Serpell
Alzheimer's disease is characterised by the self-assembly of tau and amyloid β proteins into oligomers and fibrils. Tau protein assembles into paired helical filaments (PHFs) that constitute the neurofibrillary tangles observed in neuronal cell bodies in individuals with Alzheimer's disease. The mechanism of initiation of tau assembly into PHFs is not well understood. Here we report that a truncated 95-amino acid tau fragment (corresponding to residues 297-391 of full-length tau) assembles into PHF-like fibrils in vitro without the need for other additives to initiate or template the process...
September 15, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28919059/rates-of-hippocampal-atrophy-and-presence-of-post-mortem-tdp-43-in-patients-with-alzheimer-s-disease-a-longitudinal-retrospective-study
#6
Keith A Josephs, Dennis W Dickson, Nirubol Tosakulwong, Stephen D Weigand, Melissa E Murray, Leonard Petrucelli, Amanda M Liesinger, Matthew L Senjem, Anthony J Spychalla, David S Knopman, Joseph E Parisi, Ronald C Petersen, Clifford R Jack, Jennifer L Whitwell
BACKGROUND: Post-mortem studies have not identified an association between β-amyloid or tau and rates of hippocampal atrophy in patients with Alzheimer's disease. TAR DNA binding protein 43 (TDP-43) is another protein linked to Alzheimer's disease. We aimed to investigate whether hippocampal TDP-43 is associated with increased rates of hippocampal atrophy. METHODS: In this longitudinal retrospective study, we analysed post-mortem brain tissue of all individuals with an Alzheimer's disease spectrum pathological diagnosis who had antemortem head MRI scans between Jan 1, 1999, and Dec 31, 2012, and who had been recruited into the Mayo Clinic Alzheimer's Disease Research Center, Mayo Clinic Alzheimer's Disease Patient Registry, or the Mayo Clinic Study of Aging...
September 11, 2017: Lancet Neurology
https://www.readbyqxmd.com/read/28918391/genetic-polymorphisms-associated-with-the-risk-of-concussion-in-1056-college-athletes-a-multicentre-prospective-cohort-study
#7
Thomas Roland Terrell, Ruth Abramson, Jeffery T Barth, Ellen Bennett, Robert C Cantu, Richard Sloane, Daniel T Laskowitz, David M Erlanger, Douglas McKeag, Gregory Nichols, Verle Valentine, Leslie Galloway
BACKGROUND/AIM: To evaluate the association of genetic polymorphisms APOE, APOE G-219T promoter, microtubule associated protein(MAPT)/tau exon 6 Ser(53)Pro, MAPT/tau Hist(47)Tyr, IL-6572 G/C and IL-6R(Asp)358(Ala) with the risk of concussion in college athletes. METHODS: A 23-centre prospective cohort study of 1056 college athletes with genotyping was completed between August 2003 and December 2012. All athletes completed baseline medical and concussion questionnaires, and post-concussion data were collected for athletes with a documented concussion...
September 16, 2017: British Journal of Sports Medicine
https://www.readbyqxmd.com/read/28917666/hippocampal-neurophysiology-is-modified-by-a-disease-associated-c-terminal-fragment-of-tau-protein
#8
Francesco Tamagnini, Darren A Walsh, Jon T Brown, Marie K Bondulich, Diane P Hanger, Andrew D Randall
The accumulation of cleaved tau fragments in the brain is associated with several tauopathies. For this reason, we recently developed a transgenic mouse that selectively accumulates a C-Terminal 35 kDa human tau fragment (Tau35). These animals develop progressive motor and spatial memory impairment, paralleled by increased hippocampal glycogen synthase kinase 3β activity. In this neurophysiological study, we focused on the CA1 subfield of the hippocampus, a brain area involved in memory encoding. The accumulation of Tau35 results in a significant increase of short-term facilitation of the synaptic response in the theta frequency range (10 Hz), without affecting basal synaptic transmission and long-term synaptic plasticity...
July 20, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28916533/sex-differences-in-the-prevalence-of-genetic-mutations-in-ftd-and-als-a-meta-analysis
#9
REVIEW
Ashley F Curtis, Mario Masellis, Ging-Yuek Robin Hsiung, Rahim Moineddin, Kathy Zhang, Bonnie Au, Geneva Millett, Ian Mackenzie, Ekaterina Rogaeva, Mary C Tierney
OBJECTIVE: To conduct a meta-analysis that investigates sex differences in the prevalence of mutations in the 3 most common genes that cause amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)-chromosome 9 open reading frame 72 (C9orf72), progranulin (GRN), or microtubule-associated protein tau (MAPT)-in patients clinically diagnosed with these conditions. METHODS: MEDLINE, EMBASE, and PsycINFO databases were searched (inception to June 30, 2016)...
September 15, 2017: Neurology
https://www.readbyqxmd.com/read/28915852/a-novel-frameshift-grn-mutation-results-in-frontotemporal-lobar-degeneration-with-a-distinct-clinical-phenotype-in-two-siblings-case-report-and-literature-review
#10
Takashi Hosaka, Kazuhiro Ishii, Takeshi Miura, Naomi Mezaki, Kensaku Kasuga, Takeshi Ikeuchi, Akira Tamaoka
BACKGROUND: Progranulin gene (GRN) mutations are major causes of frontotemporal lobar degeneration. To date, 68 pathogenic GRN mutations have been identified. However, very few of these mutations have been reported in Asians. Moreover, some GRN mutations manifest with familial phenotypic heterogeneity. Here, we present a novel GRN mutation resulting in frontotemporal lobar degeneration with a distinct clinical phenotype, and we review reports of GRN mutations associated with familial phenotypic heterogeneity...
September 15, 2017: BMC Neurology
https://www.readbyqxmd.com/read/28914736/update-on-tauopathies
#11
Thibaud Lebouvier, Florence Pasquier, Luc Buée
PURPOSE OF REVIEW: The purpose of this review is to provide an update on the role of tau beyond the stabilization of microtubules and on the clinical, pathological, diagnostic and therapeutic aspects of tauopathies. RECENT FINDINGS: Beyond its function as a microtubule-associated tau protein, tau is also involved in gene regulation, signal transduction and metabolism. Experimental models allow for the development of new diagnostic and therapeutic tools. Tauopathies encompass different disorders that may manifest with various clinical syndromes...
September 13, 2017: Current Opinion in Neurology
https://www.readbyqxmd.com/read/28914734/revisiting-the-concept-of-amyotrophic-lateral-sclerosis-as-a-multisystems-disorder-of-limited-phenotypic-expression
#12
Michael J Strong
PURPOSE OF REVIEW: The current review will examine the contemporary evidence that amyotrophic lateral sclerosis (ALS) is a syndrome in which the unifying feature is a progressive loss of upper and lower motor neuron function. RECENT FINDINGS: Although ALS is traditionally viewed as a neurodegenerative disorder affecting the motor neurons, there is considerable phenotypic heterogeneity and widespread involvement of the central nervous system. A broad range of both causative and disease modifying genetic variants are associated with both sporadic and familial forms of ALS...
September 13, 2017: Current Opinion in Neurology
https://www.readbyqxmd.com/read/28912300/-18-f-av-1451-binding-in-vivo-mirrors-the-expected-distribution-of-tdp-43-pathology-in-the-semantic-variant-of-primary-progressive-aphasia
#13
W R Bevan-Jones, Thomas E Cope, P Simon Jones, Luca Passamonti, Young T Hong, Tim D Fryer, Robert Arnold, Kieren S J Allinson, Jonathan P Coles, Franklin I Aigbirhio, Karalyn Patterson, John T O'Brien, James B Rowe
INTRODUCTION: Semantic dementia, including the semantic variant of primary progressive aphasia (svPPA), is strongly associated with TAR-DNA binding protein 43 (TDP-43) type C pathology. It provides a useful model in which to test the specificity of in vivo binding of the putative tau ligand [(18)F]AV-1451, which is elevated in frontotemporal lobar degeneration tauopathies. METHODS AND RESULTS: Seven patients (five with svPPA and two with 'right' semantic dementia) and 12 healthy controls underwent positron emission tomography brain imaging with [(18)F]AV-1451...
September 14, 2017: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/28904986/sex-matters-repetitive-mild-traumatic-brain-injury-in-adolescent-rats
#14
David K Wright, Terence J O'Brien, Sandy R Shultz, Richelle Mychasiuk
OBJECTIVE: Whether sex differences contribute to the heterogeneity of mild traumatic brain injury (mTBI) and repeated mTBI (RmTBI) outcomes in adolescents is unknown. Therefore, this study examined changes in, and differences between, male and female rats following single mTBI and RmTBI. METHODS: Rats were given a single mTBI, RmTBI (i.e., 3x), or sham injuries. Injuries were administered using a lateral impact model that mimics forces common in human mTBI. After the final injury, rats underwent extensive behavioral testing to examine cognition, motor function, and anxiety- and depressive-like behavior...
September 2017: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/28902708/the-effects-of-mlc901-on-tau-phosphorylation
#15
Wei Thye Lee, Christopher Chen Li Hsian, Yun-An Lim
Tauopathies are neurodegenerative diseases that are characterized by the presence of hyperphosphorylated tau-containing neurofibrillary tangles (NFTs) in the brain and include Alzheimer's disease and frontotemporal dementia, which lack effective disease-modifying treatments. The presence of NFTs is known to correlate with cognition impairment, suggesting that targeting tau hyperphosphorylation may be therapeutically effective. MLC901 is a herbal formulation that is currently used in poststroke recovery and consists of nine herbal components...
September 11, 2017: Neuroreport
https://www.readbyqxmd.com/read/28900724/hypothalamic-dysfunction-is-related-to-sleep-impairment-and-csf-biomarkers-in-alzheimer-s-disease
#16
Claudio Liguori, Agostino Chiaravalloti, Marzia Nuccetelli, Francesca Izzi, Giuseppe Sancesario, Andrea Cimini, Sergio Bernardini, Orazio Schillaci, Nicola Biagio Mercuri, Placidi Fabio
Hypothalamus is a key brain region regulating several essential homeostatic functions, including the sleep-wake cycle. Alzheimer's disease (AD) pathology affects nuclei controlling sleep-wake rhythm sited in this brain area. Since only post-mortem studies documented the relationship between hypothalamic atrophy and sleep-wake cycle impairment, we investigated in AD patients the possible hypothalamic in vivo alteration using 2-deoxy-2-(18F) fluoro-D-glucose ([18F]FDG) positron emission tomography ([18F]FDG PET), and its correlations with sleep impairment and cerebrospinal-fluid (CSF) AD biomarkers (tau proteins and β-amyloid42)...
September 12, 2017: Journal of Neurology
https://www.readbyqxmd.com/read/28900366/tau-protein-as-a-possible-marker-of-cerebrospinal-fluid-leakage-in-cerebrospinal-fluid-rhinorrhoea-a-pilot-study
#17
Jean-Baptiste Oudart, Laure Zucchini, François-Xavier Maquart, Xavier Dubernard, Marc Labrousse, Géraldine Fiabane, Alexandra Quedreux, Fabien Litre, Laurent Ramont
INTRODUCTION: The management of posttraumatic cerebrospinal fluid (CSF) rhinorrhoea remains a clinical challenge. Cerebrospinal fistula is a dural defect responsible for possible CSF leakage into the contiguous air-filled cavities located at the skull base. The risk of central nervous system infection in these conditions is severe and can be life threatening. Consequently, a specific CSF biomarker might be used in case of difficult diagnosis of CSF rhinorrhoea. CSF Tau protein is a neuronal protein, commonly assessed for diagnosis of Alzheimer Disease (AD)...
October 15, 2017: Biochemia Medica: časopis Hrvatskoga Društva Medicinskih Biokemičara
https://www.readbyqxmd.com/read/28900205/apoe4-associated-phospholipid-dysregulation-contributes-to-development-of-tau-hyper-phosphorylation-after-traumatic-brain-injury
#18
Jiqing Cao, Farida El Gaamouch, James S Meabon, Kole D Meeker, Li Zhu, Margaret B Zhong, John Bendik, Gregory Elder, Ping Jing, Jiahong Xia, Wenjie Luo, David G Cook, Dongming Cai
The apolipoprotein E4 (ApoE4) genotype combines with traumatic brain injury (TBI) to increase the risk of developing Alzheimer's Disease (AD). However, the underlying mechanism(s) is not well-understood. We found that after exposure to repetitive blast-induced TBI, phosphoinositol biphosphate (PIP2) levels in hippocampal regions of young ApoE3 mice were elevated and associated with reduction in expression of a PIP2 degrading enzyme, synaptojanin 1 (synj1). In contrast, hippocampal PIP2 levels in ApoE4 mice did not increase after blast TBI...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28899992/depletion-of-progranulin-reduces-glun2b-containing-nmda-receptor-density-tau-phosphorylation-and-dendritic-arborization-in-mouse-primary-cortical-neurons
#19
Francesca Longhena, Michela Zaltieri, Jessica Grigoletto, Gaia Faustini, Luca La Via, Roberta Ghidoni, Luisa Benussi, Cristina Missale, PierFranco Spano, Arianna Bellucci
Loss-of-function mutations in the progranulin (PGRN) gene are a common cause of familial frontotemporal lobar degeneration (FTLD). This an age-related neurodegenerative disorder characterized by brain atrophy in the frontal and temporal lobes and with typical symptoms such as cognitive and memory impairment, profound behavioral abnormalities and personality changes, that are thought to be related to connectome dysfunctions. Recently, PGRN reduction has been found to induce a behavioural phenotype reminiscent of FTLD symptoms in mice by affecting neuron spine density and morphology, suggesting that the protein can influence neuronal structural plasticity...
September 12, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28899014/slow-wave-sleep-disruption-increases-cerebrospinal-fluid-amyloid-%C3%AE-levels
#20
Yo-El S Ju, Sharon J Ooms, Courtney Sutphen, Shannon L Macauley, Margaret A Zangrilli, Gina Jerome, Anne M Fagan, Emmanuel Mignot, John M Zempel, Jurgen A H R Claassen, David M Holtzman
See Mander et al. (doi:10.1093/awx174) for a scientific commentary on this article.Sleep deprivation increases amyloid-β, suggesting that chronically disrupted sleep may promote amyloid plaques and other downstream Alzheimer's disease pathologies including tauopathy or inflammation. To date, studies have not examined which aspect of sleep modulates amyloid-β or other Alzheimer's disease biomarkers. Seventeen healthy adults (age 35-65 years) without sleep disorders underwent 5-14 days of actigraphy, followed by slow wave activity disruption during polysomnogram, and cerebrospinal fluid collection the following morning for measurement of amyloid-β, tau, total protein, YKL-40, and hypocretin...
August 1, 2017: Brain: a Journal of Neurology
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