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https://www.readbyqxmd.com/read/27866730/hereditary-neuropathies-an-update
#1
REVIEW
T Stojkovic
Hereditary neuropathies are the most common inherited neuromuscular diseases. Charcot-Marie-Tooth (CMT) disease represents the most common form with an average prevalence ranging from 1/2500 to 1/1200, depending on the studies. To date and with the advances of the latest generation sequencing, more than 80 genes have been identified. Although the common clinical phenotype comprises a progressive distal muscle weakness and sensory loss, foot deformities and decreased or absent tendon reflexes, clinical and electrophysiological phenotypes exhibit great variability...
November 17, 2016: Revue Neurologique
https://www.readbyqxmd.com/read/27807285/the-bace1-inhibitor-verubecestat-mk-8931-reduces-cns-%C3%AE-amyloid-in-animal-models-and-in-alzheimer-s-disease-patients
#2
Matthew E Kennedy, Andrew W Stamford, Xia Chen, Kathleen Cox, Jared N Cumming, Marissa F Dockendorf, Michael Egan, Larry Ereshefsky, Robert A Hodgson, Lynn A Hyde, Stanford Jhee, Huub J Kleijn, Reshma Kuvelkar, Wei Li, Britta A Mattson, Hong Mei, John Palcza, Jack D Scott, Michael Tanen, Matthew D Troyer, Jack L Tseng, Julie A Stone, Eric M Parker, Mark S Forman
β-Amyloid (Aβ) peptides are thought to be critically involved in the etiology of Alzheimer's disease (AD). The aspartyl protease β-site amyloid precursor protein cleaving enzyme 1 (BACE1) is required for the production of Aβ, and BACE1 inhibition is thus an attractive target for the treatment of AD. We show that verubecestat (MK-8931) is a potent, selective, structurally unique BACE1 inhibitor that reduced plasma, cerebrospinal fluid (CSF), and brain concentrations of Aβ40, Aβ42, and sAPPβ (a direct product of BACE1 enzymatic activity) after acute and chronic administration to rats and monkeys...
November 2, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27790089/proteomic-substrate-identification-for-membrane-proteases-in-the-brain
#3
REVIEW
Stephan A Müller, Simone D Scilabra, Stefan F Lichtenthaler
Cell-cell communication in the brain is controlled by multiple mechanisms, including proteolysis. Membrane-bound proteases generate signaling molecules from membrane-bound precursor proteins and control the length and function of cell surface membrane proteins. These proteases belong to different families, including members of the "a disintegrin and metalloprotease" (ADAM), the beta-site amyloid precursor protein cleaving enzymes (BACE), membrane-type matrix metalloproteases (MT-MMP) and rhomboids. Some of these proteases, in particular ADAM10 and BACE1 have been shown to be essential not only for the correct development of the mammalian brain, but also for myelination and maintaining neuronal connections in the adult nervous system...
2016: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/27784770/gram-negative-bacterial-molecules-associate-with-alzheimer-disease-pathology
#4
Xinhua Zhan, Boryana Stamova, Lee-Way Jin, Charles DeCarli, Brett Phinney, Frank R Sharp
OBJECTIVE: We determined whether Gram-negative bacterial molecules are associated with Alzheimer disease (AD) neuropathology given that previous studies demonstrate Gram-negative Escherichia coli bacteria can form extracellular amyloid and Gram-negative bacteria have been reported as the predominant bacteria found in normal human brains. METHODS: Brain samples from gray and white matter were studied from patients with AD (n = 24) and age-matched controls (n = 18)...
October 26, 2016: Neurology
https://www.readbyqxmd.com/read/27696165/glial-markers-and-emotional-memory-in-rats-following-acute-cerebral-radiofrequency-exposures
#5
Amélie Barthélémy, Amandine Mouchard, Marc Bouji, Kelly Blazy, Renaud Puigsegur, Anne-Sophie Villégier
The widespread mobile phone use raises concerns on the possible cerebral effects of radiofrequency electromagnetic fields (RF EMF). Reactive astrogliosis was reported in neuroanatomical structures of adaptive behaviors after a single RF EMF exposure at high specific absorption rate (SAR, 6 W/kg). Here, we aimed to assess if neuronal injury and functional impairments were related to high SAR-induced astrogliosis. In addition, the level of beta amyloid 1-40 (Aβ 1-40) peptide was explored as a possible toxicity marker...
September 30, 2016: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/27671053/liver-transplantation-in-transthyretin-amyloidosis-characteristics-and-management-related-to-kidney-disease
#6
Ana Rocha, Luísa Lobato
Orthotopic liver transplantation (LT) was implemented as the inaugural disease-modifying therapy for hereditary transthyretin (ATTR) amyloidosis, a systemic amyloidosis mainly affecting the peripheral nervous system and heart. The first approach to pharmacologic therapy was focused on the stabilization of the TTR tetramer; following that new advent LT was assumed as the second step of treatment, for those patients whose neuropathy becomes worse after a course of pharmacologic therapy. The renal disease has been ignored in hereditary ATTR amyloidosis...
September 14, 2016: Transplantation Reviews
https://www.readbyqxmd.com/read/27618323/white-matter-diseases-with-radiologic-pathologic-correlation
#7
Nicolae Sarbu, Robert Y Shih, Robert V Jones, Iren Horkayne-Szakaly, Laura Oleaga, James G Smirniotopoulos
White matter diseases include a wide spectrum of disorders that have in common impairment of normal myelination, either by secondary destruction of previously myelinated structures (demyelinating processes) or by primary abnormalities of myelin formation (dysmyelinating processes). The pathogenesis of many white matter diseases remains poorly understood. Demyelinating disorders are the object of this review and will be further divided into autoimmune, infectious, vascular, and toxic-metabolic processes. Autoimmune processes include multiple sclerosis and related diseases: tumefactive demyelinating lesions, Balo concentric sclerosis, Marburg and Schilder variants, neuromyelitis optica (Devic disease), acute disseminated encephalomyelitis, and acute hemorrhagic leukoencephalopathy (Hurst disease)...
September 2016: Radiographics: a Review Publication of the Radiological Society of North America, Inc
https://www.readbyqxmd.com/read/27591113/vascular-cognitive-impairment-neuropathology-guidelines-vcing-the-contribution-of-cerebrovascular-pathology-to-cognitive-impairment
#8
Olivia A Skrobot, Johannes Attems, Margaret Esiri, Tibor Hortobágyi, James W Ironside, Rajesh N Kalaria, Andrew King, George A Lammie, David Mann, James Neal, Yoav Ben-Shlomo, Patrick G Kehoe, Seth Love
There are no generally accepted protocols for post-mortem assessment in cases of suspected vascular cognitive impairment. Neuropathologists from seven UK centres have collaborated in the development of a set of vascular cognitive impairment neuropathology guidelines (VCING), representing a validated consensus approach to the post-mortem assessment and scoring of cerebrovascular disease in relation to vascular cognitive impairment. The development had three stages: (i) agreement on a sampling protocol and scoring criteria, through a series of Delphi method surveys; (ii) determination of inter-rater reliability for each type of pathology in each region sampled (Gwet's AC2 coefficient); and (iii) empirical testing and validation of the criteria, by blinded post-mortem assessment of brain tissue from 113 individuals (55 to 100 years) without significant neurodegenerative disease who had had formal cognitive assessments within 12 months of death...
September 2, 2016: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/27580763/a-case-of-severe-chronic-inflammatory-demyelinating-polyradiculoneuropathy-with-monoclonal-gammopathy-of-undetermined-significance-with-alternating-immunoglobulin-class-to-igm-from-iga
#9
Shintaro Hayashi, Shun Nagamine, Kouki Makioka, Susumu Kusunoki, Koichi Okamoto
A 71-year-old woman with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) with IgA-λ monoclonal gammopathy of undetermined significance (MGUS) showed the acute development of tetraplegia, respiratory failure, and a marked fluctuation of the blood pressure. Intravenous (IV) high-dose steroid therapy (methylprednisolone: 1 g/day × 3 days), followed by oral prednisolone (PSL) (40 mg/day), and IV immunoglobulin (IVIg, 0.4 g/kg/day × 5 days) administrations resulted in the amelioration of these symptoms...
September 29, 2016: Rinshō Shinkeigaku, Clinical Neurology
https://www.readbyqxmd.com/read/27494818/effectiveness-of-minocycline-in-acute-white-matter-injury-after-intracerebral-hemorrhage
#10
Xiang Zou, Zehan Wu, Wei Zhu, Liang Chen, Ying Mao, Fan Zhao
OBJECTIVE Intracerebral hemorrhage (ICH) is a fatal disease with high morbidity and mortality, which may be followed by white matter injury (WMI) due to the local oxidizing reaction induced by iron (Fe). In this study, the authors examined the effect of the tetracycline antibiotic minocycline on Fe-induced WMI and c-Jun N-terminal kinase (JNK) activation in rats. METHODS Thirty-six male Sprague-Dawley rats underwent an intracaudate injection of saline, Fe, or Fe + minocycline. Another 36 rats had an intracaudate injection of autologous blood and were treated with minocycline or vehicle (saline)...
August 5, 2016: Journal of Neurosurgery
https://www.readbyqxmd.com/read/27401753/axonopathy-in-the-central-nervous-system-is-the-hallmark-of-mice-with-a-novel-intragenic-null-mutation-of-dystonin
#11
Frauke Seehusen, Kirsten Kiel, Stefano Jottini, Peter Wohlsein, Andre Habierski, Katharina Seibel, Tanja Vogel, Henning Urlaub, Martin Kollmar, Wolfgang Baumgärtner, Ulrike Teichmann
Dystonia musculorum is a neurodegenerative disorder caused by a mutation in the dystonin gene. It has been described in mice and humans where it is called hereditary sensory autonomic neuropathy. Mutated mice show severe movement disorders and die at the age of 3-4 weeks. This study describes the discovery and molecular, clinical, as well as pathological characterization of a new spontaneously occurring mutation in the dystonin gene in C57BL/6N mice. The mutation represents a 40-kb intragenic deletion allele of the dystonin gene on chromosome 1 with exactly defined deletion borders...
September 2016: Genetics
https://www.readbyqxmd.com/read/27393467/proteolytic-processing-of-neuregulin-1
#12
Michael Willem
Neuregulin-1 (NRG1), known also as heregulin, acetylcholine receptor inducing activity (ARIA), glial growth factor (GGF), or sensory and motor neuron derived factor (SMDF), is a key factor for many developmental processes and in adult brain. All known splice variants contain an epidermal growth factor (EGF)-like domain, which is mediating signaling via receptors of the ErbB family. In particular, NRG1 acts as an essential signaling molecule expressed on the axonal surface, where it signals to Schwann cells throughout development and regulates the thickness of the myelin sheath...
July 5, 2016: Brain Research Bulletin
https://www.readbyqxmd.com/read/27354642/effect-of-lipopolysaccharide-derived-from-pantoea-agglomerans-on-the-phagocytic-activity-of-amyloid-%C3%AE-by-primary-murine-microglial-cells
#13
Yutaro Kobayashi, Hiroyuki Inagawa, Chie Kohchi, Katsuichiro Okazaki, Ran Zhang, Gen-Ichiro Soma
BACKGROUND/AIM: Monophosphoryl lipid A, lipopolysaccharide (LPS)-derived Toll-like receptor (TLR) 4 agonist, has been shown to be effective in the prevention of Alzheimer's disease (AD) by enhancing phagocytosis of amyloid β (Aβ) by brain microglia. Our recent study demonstrated that oral administration of LPS derived from Pantoea agglomerans (LPSp) activates peritoneal macrophages and enhances the phagocytic activity via TLR4 signaling pathway; however, the effect of LPSp on Aβ phagocytosis in microglia is still unknown...
July 2016: Anticancer Research
https://www.readbyqxmd.com/read/27306650/oestrogens-and-progestagens-synthesis-and-action-in-the-brain
#14
REVIEW
M F Rossetti, M J Cambiasso, M A Holschbach, R Cabrera
When steroids, such as pregnenolone, progesterone and oestrogen, are synthesised de novo in neural tissues, they are more specifically referred to as neurosteroids. These neurosteroids bind specific receptors to promote essential brain functions. Pregnenolone supports cognition and protects mouse hippocampal cells against glutamate and amyloid peptide-induced cell death. Progesterone promotes myelination, spinogenesis, synaptogenesis, neuronal survival and dendritic growth. Allopregnanolone increases hippocampal neurogenesis, neuronal survival and cognitive functions...
July 2016: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/27199760/calcium-sensing-receptors-of-human-neural-cells-play-crucial-roles-in-alzheimer-s-disease
#15
REVIEW
Anna Chiarini, Ubaldo Armato, Daisong Liu, Ilaria Dal Prà
In aged subjects, late-onset Alzheimer's disease (LOAD) starts in the lateral entorhinal allocortex where a failure of clearance mechanisms triggers an accumulation of neurotoxic amyloid-β42 oligomers (Aβ42-os). In neurons and astrocytes, Aβ42-os enhance the transcription of Aβ precursor protein (APP) and β-secretase/BACE1 genes. Thus, by acting together with γ-secretase, the surpluses of APP and BACE1 amplify the endogenous production of Aβ42-os which pile up, damage mitochondria, and are oversecreted...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27129150/myelin-injury-induces-axonal-transport-impairment-but-not-ad-like-pathology-in-the-hippocampus-of-cuprizone-fed-mice
#16
Junjun Sun, Hong Zhou, Feng Bai, Qingguo Ren, Zhijun Zhang
Both multiple sclerosis (MS) and Alzheimer's disease (AD) are progressive neurological disorders with myelin injury and memory impairment. However, whether myelin impairment could cause AD-like neurological pathology remains unclear. To explore neurological pathology following myelin injury, we assessed cognitive function, the expression of myelin proteins, axonal transport-associated proteins, axonal structural proteins, synapse-associated proteins, tau and beta amyloid and the status of neurons, using the cuprizone mouse model of demyelination...
May 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27125744/klotho-is-a-neuroprotective-and-cognition-enhancing-protein
#17
C R Abraham, P C Mullen, T Tucker-Zhou, C D Chen, E Zeldich
In this chapter, we will describe what has been learned about Klotho and its potential functions in the brain. Klotho is localized in the choroid plexus and, to a lesser extent, in hippocampal neurons. Cognitive decline is a common issue in human aging affecting over 50% of the population. This cognitive decline can also be seen in animal models such as the Rhesus monkey. A long-term study undertaken by our lab demonstrated that normal brain aging in rhesus monkeys and other animal models is associated with a significant downregulation of Klotho expression...
2016: Vitamins and Hormones
https://www.readbyqxmd.com/read/27065055/interleukin-il-8-immunoreactivity-of-injured-axons-and-surrounding-oligodendrocytes-in-traumatic-head-injury
#18
Takahito Hayashi, Kazutoshi Ago, Takuma Nakamae, Eri Higo, Mamoru Ogata
Interleukin (IL)-8 has been suggested to be a positive regulator of myelination in the central nervous system, in addition to its principal role as a chemokine for neutrophils. Immunostaining for beta-amyloid precursor protein (AβPP) is an effective tool for detecting traumatic axonal injury, although AβPP immunoreactivity can also indicate axonal injury due to hypoxic causes. In this study, we examined IL-8 and AβPP immunoreactivity in sections of corpus callosum obtained from deceased patients with blunt head injury and from equivalent control tissue...
June 2016: Forensic Science International
https://www.readbyqxmd.com/read/26971933/decreased-myelinated-fibers-in-the-hippocampal-dentate-gyrus-of-the-tg2576-mouse-model-of-alzheimer-s-disease
#19
Wei Lu, Shu Yang, Lei Zhang, Lin Chen, Feng-Lei Chao, Yan-Min Luo, Qian Xiao, Heng-Wei Gu, Rong Jiang, Yong Tang
Alzheimer's disease (AD), the most common cause of dementia in the elderly, is characterized by deficits in cognition and memory. Although amyloid-β (Aβ) accumulation is known to be the earliest pathological event that triggers subsequent neurodegeneration, how Aβ accumulation causes behavioral deficits remains incompletely understood. In this study, using the Morris water maze test, ELISA and stereological methods, we examined spatial learning and memory performance, the soluble Aβ concentration and the myelination of fibers in the hippocampus of 4-, 6-, 8- and 10-month-old Tg2576 AD model mice...
2016: Current Alzheimer Research
https://www.readbyqxmd.com/read/26922972/the-relation-between-canine-cognitive-dysfunction-and-age-related-brain-lesions
#20
Makiko Ozawa, James K Chambers, Kazuyuki Uchida, Hiroyuki Nakayama
Canine cognitive dysfunction (CCD) is a syndrome that manifests itself in abnormal behaviors, such as disorientation and wandering. β-amyloid deposition in the brain, including the senile plaque (SP) and cerebral amyloid angiopathy (CAA), has been suggested as a major cause of the syndrome. However, the pathological significance of β-amyloid deposition in CCD dogs remains unclear. The present study was conducted using 16 dogs aged 10 years or older to clarify the relationship between the age-related histopathological lesions, such as β-amyloid deposition, in the brain and the clinical symptoms of CCD as evaluated in a questionnaire previously established in a large survey...
July 1, 2016: Journal of Veterinary Medical Science
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