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https://www.readbyqxmd.com/read/28634551/mechanisms-and-consequences-of-dopamine-depletion-induced-attenuation-of-the-spinophilin-neurofilament-medium-interaction
#1
Andrew C Hiday, Michael C Edler, Asma B Salek, Cameron W Morris, Morrent Thang, Tyler J Rentz, Kristie L Rose, Lisa M Jones, Anthony J Baucum
Signaling changes that occur in the striatum following the loss of dopamine neurons in the Parkinson disease (PD) are poorly understood. While increases in the activity of kinases and decreases in the activity of phosphatases have been observed, the specific consequences of these changes are less well understood. Phosphatases, such as protein phosphatase 1 (PP1), are highly promiscuous and obtain substrate selectivity via targeting proteins. Spinophilin is the major PP1-targeting protein enriched in the postsynaptic density of striatal dendritic spines...
2017: Neural Plasticity
https://www.readbyqxmd.com/read/28631955/cerebrospinal-fluid-neurofilament-light-concentration-in-motor-neuron-disease-and-frontotemporal-dementia-predicts-survival
#2
Tobias Skillbäck, Niklas Mattsson, Kaj Blennow, Henrik Zetterberg
OBJECTIVE: To aid diagnostics, patient stratification and studies seeking to find treatments for the related diseases motor neuron disease (MND) and frontotemporal dementia (FTD), there is a need to establish a way to assess disease severity and the amount of ongoing neurodegeneration. Previous studies have suggested that cerebrospinal fluid (CSF) neurofilament light (NFL) may serve this purpose. METHODS: We cross-referenced the Swedish mortality registry with the laboratory database at Sahlgrenska University Hospital to produce a dataset of CSF NFL concentrations and mortality information for 715 MND patients, 87 FTD patients, and 107 healthy controls...
February 6, 2017: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration
https://www.readbyqxmd.com/read/28629249/increase-of-neuronal-injury-markers-tau-and-neurofilament-light-proteins-in-umbilical-blood-after-intrapartum-asphyxia
#3
Hanna Toorell, Henrik Zetterberg, Blennow, Karin Sävman, Henrik Hagberg
Fetal asphyxia remains a clinical problem resulting in life-long neurologic disabilities. We urgently need more accurate early predictive markers to direct the clinician when to provide neuroprotective therapy. In the present study, we analyzed the neuronal proteins Tau and neurofilament light proteins in umbilical blood of 10 cases of severe-moderate intrapartum asphyxia and in 18 control cases. The levels of both Tau and neurofilament were significantly higher after asphyxia and it appeared to be a correlation between the levels of the biomarkers and the severity of the insult...
June 19, 2017: Journal of Maternal-fetal & Neonatal Medicine
https://www.readbyqxmd.com/read/28628244/phosphorylated-neurofilament-heavy-chain-a-biomarker-of-survival-for-c9orf72-associated-amyotrophic-lateral-sclerosis
#4
Tania F Gendron, Lillian M Daughrity, Michael G Heckman, Nancy N Diehl, Joanne Wuu, Timothy M Miller, Pau Pastor, John Q Trojanowski, Murray Grossman, James D Berry, William T Hu, Antonia Ratti, Michael Benatar, Vincenzo Silani, Jonathan D Glass, Mary Kay Floeter, Andreas Jeromin, Kevin B Boylan, Leonard Petrucelli
As potential treatments for C9ORF72-associated amyotrophic lateral sclerosis (c9ALS) approach clinical trials, the identification of prognostic biomarkers for c9ALS becomes a priority. We show that levels of phosphorylated neurofilament heavy chain (pNFH) in cerebrospinal fluid (CSF) predict disease status and survival in c9ALS patients, and are largely stable over time. Moreover, c9ALS patients exhibit higher pNFH levels, more rapid disease progression, and shorter survival after disease onset than ALS patients without C9ORF72 expansions...
June 19, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28627962/plasma-neurofilament-light-chain-levels-in-patients-with-ms-switching-from-injectable-therapies-to-fingolimod
#5
Fredrik Piehl, Ingrid Kockum, Mohsen Khademi, Kaj Blennow, Jan Lycke, Henrik Zetterberg, Tomas Olsson
BACKGROUND: Neurofilament light chain (NFL) is a cerebrospinal fluid (CSF) marker of neuroaxonal damage in multiple sclerosis (MS). OBJECTIVE: To determine the correlation of NFL in CSF and serum/plasma, and in plasma after switching from injectable MS therapies to fingolimod. METHODS: A first cohort consisted of MS patients ( n = 39) and neurological disease controls ( n = 27) where CSF and plasma/serum had been collected for diagnostic purposes...
June 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28627021/superficial-papular-neuroma-case-series-of-a-new-entity-r2
#6
Stephanie J T Chen, Rajiv M Patel, Christine P Hans, May P Chan, Douglas R Fullen
BACKGROUND: Dermal neural lesions arise in various circumstances and may be difficult to classify. METHODS: We describe the clinical, histopathologic and immunophenotypic features of a series of terminally-differentiated neural lesions not described previously, to our knowledge. RESULTS: Four cases from men aged 58-66 years were included. Some lesions reportedly bled, but no inciting trauma or prior biopsies were reported. None recurred after biopsy, with follow-up ranging from 19 to 113 months...
June 19, 2017: Journal of Cutaneous Pathology
https://www.readbyqxmd.com/read/28622692/motor-deficits-are-independent-of-axonopathy-in-an-alzheimer-s-disease-mouse-model-of-tgcrnd8-mice
#7
Qiuju Yuan, Jian Yang, Wutian Wu, Zhi-Xiu Lin
There have been an increasing number of reports of non-cognitive symptoms in Alzheimer's disease (AD). Some symptoms are associated with the loss of motor functions, e.g. gait disturbances, disturbed activity level and balance. Consistent with clinical findings, several AD mouse models harboring amyloid pathology develop motor impairment. Although the factors that contribute to the motor deficits have not yet been determined, it has been suggested that axonopathy is one of the key factors that may contribute to this particular feature of the disease...
June 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28617379/-immunohistochemical-characteristics-of-the-substantia-nigra-neurons-of-the-human
#8
D E Korzhevskii, I P Grigor'ev, E G Sukhorukova, V V Gusel'nikova
AIM: To determine the cytochemical characteristics of unchanged neurons of the human substantia nigra using a wide range of immunocytochemical markers some of which (glutamate decarboxylase-65, PGP 9.5, non-phosphorylated neurofilament proteins, alpa-tubulin) have never been used for study of human dopaminergic neurons. MATERIAL AND METHODS: Fragments of human midbrain (17 men and women, aged from 28 to 78 years) from the archives of the Department of General and Specific Morphology of the Institute of Experimental Medicine were used...
2017: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/28604235/discovery-validation-and-optimization-of-cerebrospinal-fluid-biomarkers-for-use-in-parkinson-s-disease
#9
Lucia Farotti, Silvia Paciotti, Anna Tasegian, Paolo Eusebi, Lucilla Parnetti
Parkinson's disease (PD) is a complex and phenotypically heterogeneous neurodegenerative disease, for which the diagnosis is mainly based on clinical parameters (even if neuroimaging plays a role in diagnostic assessment); as a consequence, misdiagnosis is common, especially in early stages. Thus, there is an urgent need of having available biomarkers in order to achieve an early and accurate diagnosis. Since molecular changes in the brain are reliably and timely reflected in cerebrospinal fluid (CSF), CSF represents an ideal source for biomarkers of different pathophysiological processes characterizing the disease since its early phases...
June 19, 2017: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/28601473/neurofilament-light-protein-in-blood-as-a-potential-biomarker-of-neurodegeneration-in-huntington-s-disease-a-retrospective-cohort-analysis
#10
Lauren M Byrne, Filipe B Rodrigues, Kaj Blennow, Alexandra Durr, Blair R Leavitt, Raymund A C Roos, Rachael I Scahill, Sarah J Tabrizi, Henrik Zetterberg, Douglas Langbehn, Edward J Wild
BACKGROUND: Blood biomarkers of neuronal damage could facilitate clinical management of and therapeutic development for Huntington's disease. We investigated whether neurofilament light protein NfL (also known as NF-L) in blood is a potential prognostic marker of neurodegeneration in patients with Huntington's disease. METHODS: We did a retrospective analysis of healthy controls and carriers of CAG expansion mutations in HTT participating in the 3-year international TRACK-HD study...
June 7, 2017: Lancet Neurology
https://www.readbyqxmd.com/read/28600739/association-of-longitudinal-white-matter-degeneration-and-cerebrospinal-fluid-biomarkers-of-neurodegeneration-inflammation-and-alzheimer-s-disease-in-late-middle-aged-adults
#11
Annie M Racine, Andrew P Merluzzi, Nagesh Adluru, Derek Norton, Rebecca L Koscik, Lindsay R Clark, Sara E Berman, Christopher R Nicholas, Sanjay Asthana, Andrew L Alexander, Kaj Blennow, Henrik Zetterberg, Won Hwa Kim, Vikas Singh, Cynthia M Carlsson, Barbara B Bendlin, Sterling C Johnson
Alzheimer's disease (AD) is characterized by substantial neurodegeneration, including both cortical atrophy and loss of underlying white matter fiber tracts. Understanding longitudinal alterations to white matter may provide new insights into trajectories of brain change in both healthy aging and AD, and fluid biomarkers may be particularly useful in this effort. To examine this, 151 late-middle-aged participants enriched with risk for AD with at least one lumbar puncture and two diffusion tensor imaging (DTI) scans were selected for analysis from two large observational and longitudinally followed cohorts...
June 9, 2017: Brain Imaging and Behavior
https://www.readbyqxmd.com/read/28600442/tracking-and-predicting-disease-progression-in-progressive-supranuclear-palsy-csf-and-blood-biomarkers
#12
REVIEW
Edwin Jabbari, Henrik Zetterberg, Huw R Morris
Progressive supranuclear palsy (PSP) is a rare and progressive neurodegenerative condition characterised pathologically by neuronal cell loss due to abnormal tau deposits. Clinically, the condition manifests as parkinsonism with the addition of progressive balance, speech, swallowing, eye movement and cognitive impairment, ultimately leading to death. Measuring change over time in neurodegenerative conditions is central to defining the effects of therapeutic intervention and disease biology. The current gold standard for measuring clinical disease progression in PSP is the PSP Rating Scale score...
June 9, 2017: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/28598844/combustion-derived-nanoparticles-in-key-brain-target-cells-and-organelles-in-young-urbanites-culprit-hidden-in-plain-sight-in-alzheimer-s-disease-development
#13
Angélica González-Maciel, Rafael Reynoso-Robles, Ricardo Torres-Jardón, Partha S Mukherjee, Lilian Calderón-Garcidueñas
Millions of children and young adults are exposed to fine particulate matter (PM2.5) and ozone, associated with Alzheimer's disease (AD) risk. Mexico City (MC) children exhibit systemic and brain inflammation, low cerebrospinal fluid (CSF) Aβ1-42, breakdown of nasal, olfactory, alveolar-capillary, duodenal, and blood-brain barriers, volumetric and metabolic brain changes, attention and short-term memory deficits, and hallmarks of AD and Parkinson's disease. Airborne iron-rich strongly magnetic combustion-derived nanoparticles (CDNPs) are present in young urbanites' brains...
June 3, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28598205/neurofilament-light-chain-protein-as-a-marker-of-neuronal-injury-review-of-its-use-in-hiv-1-infection-and-reference-values-for-hiv-negative-controls
#14
Aylin Yilmaz, Kaj Blennow, Lars Hagberg, Staffan Nilsson, Richard W Price, Judith Schouten, Serena Spudich, Jonathan Underwood, Henrik Zetterberg, Magnus Gisslén
Several CSF biomarkers of neuronal injury have been studied in people living with HIV. At this time, the most useful is the light subunit of the neurofilament protein (NFL). This major structural component of myelinated axons is essential to maintain axonal caliber and to facilitate effective nerve conduction. CSF concentrations of NFL provide a sensitive marker of CNS injury in a number of neurological diseases, including HIV-related neuronal injury. Areas Covered: In this review, the authors describe CSF NFL concentrations across the spectrum of HIV-infection, from its early acute phase to severe immunosuppression, with and without neurological conditions, and with and without antiretroviral treatment (n = 516)...
June 14, 2017: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/28595357/the-alzheimer-s-disease-transcriptome-mimics-the-neuroprotective-signature-of-igf-1-receptor-deficient-neurons
#15
Caroline George, Géraldine Gontier, Philippe Lacube, Jean-Christophe François, Martin Holzenberger, Saba Aïd
Seminal studies using post-mortem brains of patients with Alzheimer's disease evidenced aberrant insulin-like growth factor 1 receptor (IGF1R) signalling. Addressing causality, work in animal models recently demonstrated that long-term suppression of IGF1R signalling alleviates Alzheimer's disease progression and promotes neuroprotection. However, the underlying mechanisms remain largely elusive. Here, we showed that genetically ablating IGF1R in neurons of the ageing brain efficiently protects from neuroinflammation, anxiety and memory impairments induced by intracerebroventricular injection of amyloid-β oligomers...
June 8, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28595035/n-methyl-d-aspartate-receptors-mediate-epilepsy-induced-axonal-impairment-and-tau-phosphorylation-via-activating-glycogen-synthase-kinase-3%C3%AE-and-cyclin-dependent-kinase-5
#16
Xi Liu, Shu Ou, Maojia Yin, Tao Xu, Teng Wang, Ying Liu, Xueying Ding, Xinyuan Yu, Jinxian Yuan, Hao Huang, Xiuhang Zhang, Xinjie Tan, Lifen Chen, Yangmei Chen
The mechanism of epilepsy-induced axonal impairment is poorly understood. N-methyl-D-aspartate receptors (NMDARs) play important roles in epilepsy and mediate structural and functional axonal impairment. GSK-3β and Cdk5 affect axons and are regulated by NMDARs, while their roles in epilepsy-induced axonal impairment are unclear. We demonstrated that axonal impairment is characterized by neurofilament heavy (NFH) reduction, amyloid precursor protein (APP) accumulation, and increased tau phosphorylation accompanied by a decrease of total tau in temporal lobe epilepsy (TLE) patients and pentylenetetrazol (PTZ)-kindled rats...
April 2017: Discovery Medicine
https://www.readbyqxmd.com/read/28592456/csf-sapp%C3%AE-ykl-40-and-neurofilament-light-in-frontotemporal-lobar-degeneration
#17
Daniel Alcolea, Eduard Vilaplana, Marc Suárez-Calvet, Ignacio Illán-Gala, Rafael Blesa, Jordi Clarimón, Albert Lladó, Raquel Sánchez-Valle, José L Molinuevo, Guillermo García-Ribas, Yaroslau Compta, María José Martí, Gerard Piñol-Ripoll, Guillermo Amer-Ferrer, Aina Noguera, Ana García-Martín, Juan Fortea, Alberto Lleó
OBJECTIVE: To analyze the clinical utility of 3 CSF biomarkers and their structural imaging correlates in a large cohort of patients with different dementia and parkinsonian syndromes within the spectrum of frontotemporal lobar degeneration (FTLD). METHODS: We analyzed 3 CSF biomarkers (YKL-40, soluble β fragment of amyloid precursor protein [sAPPβ], neurofilament light [NfL]) and core Alzheimer disease (AD) biomarkers (β-amyloid1-42, total tau, phosphorylated tau) in patients with FTLD-related clinical syndromes (n = 159): behavioral variant of frontotemporal dementia (n = 68), nonfluent (n = 23) and semantic (n = 19) variants of primary progressive aphasia, progressive supranuclear palsy (n = 28), and corticobasal syndrome (n = 21)...
June 7, 2017: Neurology
https://www.readbyqxmd.com/read/28584012/nefm-neurofilament-medium-polypeptide-a-marker-for-zona-glomerulosa-cells-in-human-adrenal-inhibits-d1r-dopamine-d1-receptor-mediated-secretion-of-aldosterone
#18
Carmela Maniero, Sumedha Garg, Wanfeng Zhao, Timothy Isaac Johnson, Junhua Zhou, Mark Gurnell, Morris J Brown
Heterogeneity among aldosterone-producing adenomas (APAs) has been highlighted by the discovery of somatic mutations. KCNJ5 mutations predominate in large zona fasciculata (ZF)-like APAs; mutations in CACNA1D, ATP1A1, ATP2B3, and CTNNB1 are more likely to be found in small zona glomerulosa (ZG)-like APAs. Microarray comparison of KCNJ5 mutant versus wild-type APAs revealed significant differences in transcriptomes. NEFM, encoding a neurofilament subunit which is a D1R (dopamine D1 receptor)-interacting protein, was 4-fold upregulated in ZG-like versus ZF-like APAs and 14-fold more highly expressed in normal ZG versus ZF...
June 5, 2017: Hypertension
https://www.readbyqxmd.com/read/28561950/poly-n-4-aminobutyl-acrylamide-as-mimetic-polylysine-for-improving-survival-and-differentiation-of-cerebellar-granule-neurons
#19
Yu-Hsin Wang, Shao-Hsuan Chang, Daxen Mau-Hsu, Jyh-Horng Wang, Tai-Horng Young
Poly(N-(4-aminobutyl)-acrylamide) (P4Am) and poly-d-lysine (PDL) possess the same butylamine side chain. The main difference is the peptide structure, which is in the main chain of PDL but in the side chain of P4Am. PDL has been extensively used in the preparation of neuronal cultures. We assumed neurons are sensitive enough to distinguish such structure difference so these two cationic polymers were compared at serial coating concentrations for culturing cerebellar granule neurons from 7-day-old Wistar rats in this study...
May 31, 2017: Journal of Biomedical Materials Research. Part B, Applied Biomaterials
https://www.readbyqxmd.com/read/28554564/the-third-wave-intermediate-filaments-in-the-maturing-nervous-system
#20
REVIEW
Matthew T K Kirkcaldie, Samuel T Dwyer
Intermediate filaments are critical for the extreme structural specialisations of neurons, providing integrity in dynamic environments and efficient communication along axons a metre or more in length. As neurons mature, an initial expression of nestin and vimentin gives way to α-internexin and the neurofilament triplet proteins, substituted by peripherin in axons outside the CNS, physically consolidating axons as they elongate and find their targets. Once connection is established, these proteins are transported, assembled, stabilised and modified, structurally transforming axons and dendrites as they acquire their full function...
May 26, 2017: Molecular and Cellular Neurosciences
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