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https://www.readbyqxmd.com/read/28539871/protein-quality-control-and-the-amyotrophic-lateral-sclerosis-frontotemporal-dementia-continuum
#1
Hamideh Shahheydari, Audrey Ragagnin, Adam K Walker, Reka P Toth, Marta Vidal, Cyril J Jagaraj, Emma R Perri, Anna Konopka, Jessica M Sultana, Julie D Atkin
Protein homeostasis, or proteostasis, has an important regulatory role in cellular function. Protein quality control mechanisms, including protein folding and protein degradation processes, have a crucial function in post-mitotic neurons. Cellular protein quality control relies on multiple strategies, including molecular chaperones, autophagy, the ubiquitin proteasome system, endoplasmic reticulum (ER)-associated degradation (ERAD) and the formation of stress granules (SGs), to regulate proteostasis. Neurodegenerative diseases are characterized by the presence of misfolded protein aggregates, implying that protein quality control mechanisms are dysfunctional in these conditions...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28534652/a-review-of-the-evidence-of-zolpidem-efficacy-in-neurological-disability-after-brain-damage-due-to-stroke-trauma-and-hypoxia-a-justification-of-further-clinical-trials
#2
J A Sutton, R P Clauss
During 15 years, 23 clinical reports and 6 studies have demonstrated associations between sub-sedative doses of zolpidem and recoveries from brain damage due to strokes, trauma and hypoxia. Clinical findings include unexpected awakenings from vegetative states and regressions of stroke symptoms after dosing that disappear during elimination and reappear on repeat dosing. Initially single-photon emission computed tomography scans showed improved perfusion within, around and distant from infarctions. Then positron emission tomography scans and electroencephalography detected renewed metabolic and neuronal activity...
May 23, 2017: Brain Injury: [BI]
https://www.readbyqxmd.com/read/28533210/specific-biomarkers-for-c9orf72-ftd-als-could-expedite-the-journey-towards-effective-therapies
#3
Rubika Balendra, Thomas G Moens, Adrian M Isaacs
No abstract text is available yet for this article.
May 22, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28529873/white-matter-hyperintensities-are-seen-only-in-grn-mutation-carriers-in-the-genfi-cohort
#4
Carole H Sudre, Martina Bocchetta, David Cash, David L Thomas, Ione Woollacott, Katrina M Dick, John van Swieten, Barbara Borroni, Daniela Galimberti, Mario Masellis, Maria Carmela Tartaglia, James B Rowe, Caroline Graff, Fabrizio Tagliavini, Giovanni Frisoni, Robert Laforce, Elizabeth Finger, Alexandre de Mendonça, Sandro Sorbi, Sébastien Ourselin, M Jorge Cardoso, Jonathan D Rohrer
Genetic frontotemporal dementia is most commonly caused by mutations in the progranulin (GRN), microtubule-associated protein tau (MAPT) and chromosome 9 open reading frame 72 (C9orf72) genes. Previous small studies have reported the presence of cerebral white matter hyperintensities (WMH) in genetic FTD but this has not been systematically studied across the different mutations. In this study WMH were assessed in 180 participants from the Genetic FTD Initiative (GENFI) with 3D T1- and T2-weighed magnetic resonance images: 43 symptomatic (7 GRN, 13 MAPT and 23 C9orf72), 61 presymptomatic mutation carriers (25 GRN, 8 MAPT and 28 C9orf72) and 76 mutation negative non-carrier family members...
2017: NeuroImage: Clinical
https://www.readbyqxmd.com/read/28527630/diagnostic-accuracy-of-csf-neurofilament-light-chain-protein-in-the-biomarker-guided-classification-system-for-alzheimer-s-disease
#5
Simone Lista, Nicola Toschi, Filippo Baldacci, Henrik Zetterberg, Kaj Blennow, Ingo Kilimann, Stefan J Teipel, Enrica Cavedo, Antonio Melo Dos Santos, Stéphane Epelbaum, Foudil Lamari, Bruno Dubois, Roberto Floris, Francesco Garaci, Harald Hampel
We assessed the diagnostic accuracy of cerebrospinal fluid (CSF) neurofilament light chain (NFL) protein in the classification of patients with Alzheimer's disease (AD) and cognitively healthy control individuals (HCs) and patients with frontotemporal dementia (FTD) as comparisons. Particularly, we tested the performance of CSF NFL concentration in differentiating patient groups stratified by fluid biomarker profiles, independently of the severity of cognitive impairment (mild cognitive impairment (MCI) and AD dementia individuals), using a biomarker-guided descriptive classification system for AD...
May 17, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28522837/age-related-penetrance-of-the-c9orf72-repeat-expansion
#6
Natalie A Murphy, Karissa C Arthur, Pentti J Tienari, Henry Houlden, Adriano Chiò, Bryan J Traynor
A pathogenic hexanucleotide repeat expansion within the C9orf72 gene has been identified as the major cause of two neurodegenerative syndromes, amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). This mutation is known to have incomplete penetrance, with some patients developing disease in their twenties and a small portion of carriers surviving to their ninth decade without developing symptoms. Describing penetrance by age among C9orf72 carriers and identifying parameters that alter onset age are essential to better understanding this locus and to enhance predictive counseling...
May 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28515555/quantitative-balance-and-gait-measurement-in-patients-with-frontotemporal-dementia-and-alzheimer-diseases-a-pilot-study
#7
Selva Ganapathy Velayutham, Sadanandavalli Retnaswami Chandra, Srikala Bharath, Ravi Girikamatha Shankar
INTRODUCTION: Alzhiemers disease and Frontotemporal dementia are common neurodegenerative dementias with a wide prevalence. Falls are a common cause of morbidity in these patients. Identifying subclinical involvement of these parameters might serve as a tool in differential analysis of these distinct parameters involved in these conditions and also help in planning preventive strategies to prevent falls. PATIENTS AND METHODS: Eight patients in age and gender matched patients in each group were compared with normal controls...
March 2017: Indian Journal of Psychological Medicine
https://www.readbyqxmd.com/read/28515553/long-loop-reflex-2-in-patients-with-cortical-dementias-a-pilot-study
#8
Sadanandavalli Retnaswami Chandra, Thomas Gregor Isaac, Mahesh Mane, Srikala Bharath, B C Nagaraju
INTRODUCTION: Dementia is a major public health problem and it appears to be a global epidemic. The prevalence is doubling every 5 years and it is expected that 70% of persons above 60 years will live in developing countries by 2020 and 15% of them are likely to suffer from dementia. Disease modifying treatments work only if initiated very early; however, diagnostic tools are not always able to clearly differentiate the different types in very early stage. Therefore, inexpensive and easily available biomarkers are needed to know if collectively they will improve the sensitivity of specific diagnosis...
March 2017: Indian Journal of Psychological Medicine
https://www.readbyqxmd.com/read/28515546/use-of-jonkman-et-al-score-for-visual-quantification-of-electroencephalography-as-a-tool-to-assess-disease-severity-in-cortical-dementias
#9
R Kiran Kumar, Sadanandavalli Retnaswami Chandra, Girish B Kulkarni, Rose Dawn Bharath
OBJECTIVES: To study electroencephalography (EEG) changes in patients with cortical dementias (Alzheimer's disease [AD] and frontotemporal dementia (FTD). (1) To correlate EEG changes with clinical severity of dementia as assessed by rating scales. (2) To correlate global gray matter volume (GGMV) with EEG scores and clinical severity rating scales. PATIENTS AND METHODS: This is a prospective cross-sectional study involving patients fulfilling the criteria for Probable AD and FTD...
March 2017: Indian Journal of Psychological Medicine
https://www.readbyqxmd.com/read/28501823/cerebellar-atrophy-in-neurodegeneration-a-meta-analysis
#10
REVIEW
Helena M Gellersen, Christine C Guo, Claire O'Callaghan, Rachel H Tan, Saber Sami, Michael Hornberger
INTRODUCTION: The cerebellum has strong cortical and subcortical connectivity, but is rarely taken into account for clinical diagnosis in many neurodegenerative conditions, particularly in the absence of clinical ataxia. The current meta-analysis aims to assess patterns of cerebellar grey matter atrophy in seven neurodegenerative conditions (Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), multiple system atrophy (MSA), progressive supranuclear palsy (MSP))...
May 13, 2017: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/28490746/pathogenic-p62-sqstm1-mutations-impair-energy-metabolism-through-limitation-of-mitochondrial-substrates
#11
Fernando Bartolome, Noemi Esteras, Angeles Martin-Requero, Claire Boutoleau-Bretonniere, Martine Vercelletto, Audrey Gabelle, Isabelle Le Ber, Tadashi Honda, Albena T Dinkova-Kostova, John Hardy, Eva Carro, Andrey Y Abramov
Abnormal mitochondrial function has been found in patients with frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Mutations in the p62 gene (also known as SQSTM1) which encodes the p62 protein have been reported in both disorders supporting the idea of an ALS/FTD continuum. In this work the role of p62 in energy metabolism was studied in fibroblasts from FTD patients carrying two independent pathogenic mutations in the p62 gene, and in a p62-knock-down (p62 KD) human dopaminergic neuroblastoma cell line (SH-SY5Y)...
May 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28490314/pain-experience-in-dementia-subtypes-a-systematic-review
#12
Tarik T Binnekade, Janime Van Kooten, Frank Lobbezoo, Didi Rhebergen, J C Van der Wouden, Martin Smalbrugge, Erik J A Scherder
Recently, the number of studies focusing on pain in dementia has increased considerably. Still, little attention has been paid to the influence of the neuropathology of different dementia subtypes on pain experience. In 2003, a review identified several studies that indicated a relation between dementia subtype and pain experience. Now, ten years later, an update is warranted. We conducted a systematic review to identify studies that assessed pain experience and dementia subtypes by searching PubMed, Embase, PsycINFO, CINAHL, and Cochrane Library...
2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28486761/panitumumab-interaction-with-tas-102-leads-to-combinational-anticancer-effects-via-blocking-of-egfr-mediated-tumor-response-to-trifluridine
#13
Yuji Baba, Toshiya Tamura, Yoshihiko Satoh, Masamitsu Gotou, Hiroshi Sawada, Shunsuke Ebara, Kazunori Shibuya, Jumpei Soeda, Kazuhide Nakamura
Panitumumab is a monoclonal antibody developed against the human epidermal growth factor receptor (EGFR). TAS-102 is a novel chemotherapeutic agent containing trifluridine (FTD) as the active cytotoxic component. Both panitumumab and TAS-102 have been approved for the treatment of metastatic colorectal cancer. In this study, we revealed the mechanism underlying the anticancer effects of panitumumab/TAS-102 combination using preclinical models. Panitumumab/FTD co-treatment showed additive antiproliferative effects in LIM1215 and synergistic antiproliferative effects in SW48 colon cancer cells...
May 9, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28484365/wild-type-but-not-mutant-n296h-human-tau-restores-a%C3%AE-mediated-inhibition-of-ltp-in-tau-mice
#14
Mariana Vargas-Caballero, Franziska Denk, Heike J Wobst, Emily Arch, Chrysia-Maria Pegasiou, Peter L Oliver, Olivia A Shipton, Ole Paulsen, Richard Wade-Martins
Microtubule associated protein tau (MAPT) is involved in the pathogenesis of Alzheimer's disease and many forms of frontotemporal dementia (FTD). We recently reported that Aβ-mediated inhibition of hippocampal long-term potentiation (LTP) in mice requires tau. Here, we asked whether expression of human MAPT can restore Aβ-mediated inhibition on a mouse Tau(-/-) background and whether human tau with an FTD-causing mutation (N296H) can interfere with Aβ-mediated inhibition of LTP. We used transgenic mouse lines each expressing the full human MAPT locus using bacterial artificial chromosome technology...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28482638/von-economo-neuron-density-and-thalamus-volumes-in-behavioral-deficits-in-frontotemporal-dementia-cases-with-and-without-a-c9orf72-repeat-expansion
#15
Yue Yang, Glenda M Halliday, John R Hodges, Rachel H Tan
BACKGROUND: The early and selective loss of von Economo neurons in the anterior cingulate cortex has been linked to behavioral deficits in frontotemporal dementia (FTD). Importantly, whether these neurons are also targeted in patients with the C9ORF72 repeat expansion has yet to be established. This is of particular interest given the recent evidence highlighting the thalamus rather than anterior cingulate cortex as a region of significant degeneration in patients with the C9ORF72 repeat expansion...
May 5, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28481984/the-dna-damage-response-ddr-is-induced-by-the-c9orf72-repeat-expansion-in-amyotrophic-lateral-sclerosis
#16
Manal A Farg, Anna Konopka, Kai Ying Soo, Daisuke Ito, Julie D Atkin
Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disease affecting motor neurons. Hexanucleotide (GGGGCC) repeat expansions in a non-coding region of C9orf72 are the major cause of familial ALS and frontotemporal dementia (FTD) worldwide. The C9orf72 repeat expansion undergoes repeat-associated non-ATG (RAN) translation to produce five dipeptide repeat proteins (DRPs), including poly(GR) and poly(PR). Whilst it remains unclear how mutations in C9orf72 lead to neurodegeneration in ALS/FTD, dysfunction to the nucleolus and R loop formation are implicated as pathogenic mechanisms...
May 8, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28472993/humanized-monoclonal-antibody-armanezumab-specific-to-n-terminus-of-pathological-tau-characterization-and-therapeutic-potency
#17
Michael G Agadjanyan, Karen Zagorski, Irina Petrushina, Hayk Davtyan, Konstantin Kazarian, Maxim Antonenko, Joy Davis, Charles Bon, Mathew Blurton-Jones, David H Cribbs, Anahit Ghochikyan
BACKGROUND: The experience from clinical trials indicates that anti-Aβ immunotherapy could be effective in early/pre-clinical stages of AD, whereas at the late stages promoting the clearing of Aβ alone may be insufficient to halt the disease progression. At the same time, pathological tau correlates much better with the degree of dementia than Aβ deposition. Therefore, targeting pathological tau may provide a more promising approach for the treatment of advanced stages of AD. Recent data demonstrates that the N-terminal region of tau spanning aa 2-18 termed "phosphatase activation domain" that is normally hidden in the native protein in 'paperclip'-like conformation, becomes exposed in pathological tau and plays an essential role in the inhibition of fast axonal transport and in aggregation of tau...
May 5, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28462717/genetic-features-of-mapt-grn-c9orf72-and-chchd10-gene-mutations-in-chinese-patients-with-frontotemporal-dementia
#18
Xiang-Qian Che, Qian-Hua Zhao, Yue Huang, Xia Li, Ru-Jing Ren, Sheng-Di Chen, Gang Wang, Qi-Hao Guo
Mutations in microtubule associated protein tau (MAPT), progranulin (GRN), chromosome 9 open-reading frame 72 (C9orf72) and CHCHD10 genes have been reported causing frontotemporal dementia (FTD) in different populations. However, collective analysis of mutations in these four genes in Chinese FTD patients has not been reported yet. The aim of this study was to investigate the geneticfeatures of Chinese patients with MAPT, PGRN, C9orf72 or CHCHD10 gene mutations in a FTD cohort recruited from multi clinical centers in Shanghai metropolitan areas, China...
April 25, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28460069/cognitive-reserve-and-tmem106b-genotype-modulate-brain-damage-in-presymptomatic-frontotemporal-dementia-a-genfi-study
#19
Enrico Premi, Mario Grassi, John van Swieten, Daniela Galimberti, Caroline Graff, Mario Masellis, Carmela Tartaglia, Fabrizio Tagliavini, James B Rowe, Robert Laforce, Elizabeth Finger, Giovanni B Frisoni, Alexandre de Mendonça, Sandro Sorbi, Stefano Gazzina, Maura Cosseddu, Silvana Archetti, Roberto Gasparotti, Marta Manes, Antonella Alberici, Manuel J Cardoso, Martina Bocchetta, David M Cash, Sebastian Ourselin, Alessandro Padovani, Jonathan D Rohrer, Barbara Borroni
Frontotemporal dementia is a heterogeneous neurodegenerative disorder with around a third of cases having autosomal dominant inheritance. There is wide variability in phenotype even within affected families, raising questions about the determinants of the progression of disease and age at onset. It has been recently demonstrated that cognitive reserve, as measured by years of formal schooling, can counteract the ongoing pathological process. The TMEM106B genotype has also been found to be a modifier of the age at disease onset in frontotemporal dementia patients with TDP-43 pathology...
April 27, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28453695/genetic-variants-of-dna-repair-related-genes-predict-efficacy-of-tas-102-in-patients-with-refractory-metastatic-colorectal-cancer
#20
M Suenaga, M Schirripa, S Cao, W Zhang, D Yang, S Murgioni, D Rossini, F Marmorino, A Mennitto, Y Ning, S Okazaki, M D Berger, Y Miyamoto, R Gopez, A Barzi, T Yamaguchi, F Loupakis, H-J Lenz
Background: Tri-phosphorylated trifluridine (FTD) incorporation into DNA is TAS-102's main anti-tumor action. We tested whether genetic polymorphisms in homologous recombination (HR) and cell cycle checkpoint pathway for DNA repair is associated with outcomes in refractory metastatic colorectal cancer (mCRC) patients treated with TAS-102. Patients and methods: We analyzed genomic DNA extracted from 233 samples of three cohorts: an evaluation cohort of 52 patients receiving TAS-102, a validation cohort of 129 patients receiving TAS-102 and a control cohort of 52 patients receiving regorafenib...
May 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
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