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https://www.readbyqxmd.com/read/28088536/targeting-sonic-hedgehog-signaling-in-neurological-disorders
#1
REVIEW
Sita Sharan Patel, Sunil Tomar, Diksha Sharma, Neeraj Mahindroo, Malairaman Udayabanu
Sonic hedgehog (Shh) signaling influences neurogenesis and neural patterning during the development of central nervous system. Dysregulation of Shh signaling in brain leads to neurological disorders like autism spectrum disorder, depression, dementia, stroke, Parkinson's diseases, Huntington's disease, locomotor deficit, epilepsy, demyelinating disease, neuropathies as well as brain tumors. The synthesis, processing and transport of Shh ligand as well as the localization of its receptors and signal transduction in the central nervous system has been carefully reviewed...
January 11, 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/28088312/dementia-in-parkinson-s-disease
#2
REVIEW
Hasmet A Hanagasi, Zeynep Tufekcioglu, Murat Emre
Dementia can occur in a substantial number of patients with Parkinson's disease with a point prevalence close to 30%. The cognitive profile is characterized by predominant deficits in executive, visuospatial functions, attention and memory. Behavioral symptoms are frequent such as apathy, visual hallucinations and delusions. The most prominent associated pathology is Lewy body-type and biochemical deficit is cholinergic. Placebo-controlled randomized trials with cholinesterase inhibitors demonstrated modest but significant benefits in cognition, behavioral symptoms and global functions...
January 5, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28087304/sleep-and-neurodegeneration-a-critical-appraisal
#3
REVIEW
Jagan A Pillai, James B Leverenz
Sleep abnormalities are clearly recognized as distinct clinical symptom of concern in neurodegenerative disorders. Appropriate management of sleep related symptoms has a positive impact on the quality of life of patients with neurodegenerative disorders. This review provides an overview of mechanisms that are currently being considered that tie sleep with neurodegeneration. It appraises the literature regarding specific sleep changes among common neurodegenerative diseases with a focus on Alzheimer's disease and synucleinopathies (i...
January 10, 2017: Chest
https://www.readbyqxmd.com/read/28086964/anti-%C3%AE-synuclein-immunotherapy-reduces-%C3%AE-synuclein-propagation-in-the-axon-and-degeneration-in-a-combined-viral-vector-and-transgenic-model-of-synucleinopathy
#4
Brian Spencer, Elvira Valera, Edward Rockenstein, Cassia Overk, Michael Mante, Anthony Adame, Wagner Zago, Peter Seubert, Robin Barbour, Dale Schenk, Dora Games, Robert A Rissman, Eliezer Masliah
Neurodegenerative disorders such as Parkinson's Disease (PD), PD dementia (PDD) and Dementia with Lewy bodies (DLB) are characterized by progressive accumulation of α-synuclein (α-syn) in neurons. Recent studies have proposed that neuron-to-neuron propagation of α-syn plays a role in the pathogenesis of these disorders. We have previously shown that antibodies against the C-terminus of α-syn reduce the intra-neuronal accumulation of α-syn and related deficits in transgenic models of synucleinopathy, probably by abrogating the axonal transport and accumulation of α-syn in in vivo models...
January 13, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28077166/threonine-175-a-novel-pathological-phosphorylation-site-on-tau-protein-linked-to-multiple-tauopathies
#5
Alexander J Moszczynski, Wencheng Yang, Robert Hammond, Lee Cyn Ang, Michael J Strong
Microtubule associated protein tau (tau) deposition is associated with a spectrum of neurodegenerative diseases collectively termed tauopathies. We have previously shown that amyotrophic lateral sclerosis (ALS) with cognitive impairment (ALSci) is associated with tau phosphorylation at Thr(175) and that this leads to activation of GSK3β which then induces phosphorylation at tau Thr(231). This latter step leads to dissociation of tau from microtubules and pathological tau fibril formation. To determine the extent to which this pathway is unique to ALS, we have investigated the expression of pThr(175) tau and pThr(231) tau across a range of frontotemporal degenerations...
January 11, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28075568/reaction-pathways-and-kinetics-of-a-cyanobacterial-neurotoxin-%C3%AE-n-methylamino-l-alanine-bmaa-during-chlorination
#6
Yiting Chen, Wan-Ru Chen, Zhiquan Liu, Tsair-Fuh Lin
β-N-Methylamino-L-alanine (BMAA), a probable cause of the amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/PDC), or Alzheimer's disease, has been identified in more than 20 cyanobacterial genera. However, its removal and fate in drinking water has never been reported before. In this study, the reaction of BMAA with chlorine, a common drinking-water oxidant/disinfectant, was investigated. A liquid chromatograph coupled with a triple quadrupole mass spectrometer was employed to quantify BMAA and its intermediates...
January 11, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28075435/cardiac-biomarkers-predict-1-year-mortality-in-elderly-patients-undergoing-hip-fracture-surgery
#7
Spyridon Katsanos, Andreas F Mavrogenis, Nikolaos Kafkas, Celestino Sardu, Vasileios Kamperidis, Panagiota Katsanou, Dimitrios Farmakis, John Parissis
This prospective study included 152 elderly patients (mean age, 80 years; range, 72-88 years) with a hip fracture treated surgically. Comorbidities were evaluated, and B-type natriuretic peptide was measured at baseline and at postoperative days 4 and 5 in addition to troponin I. Major cardiac events were recorded, and 1-year mortality was assessed. Comorbidity models with the important multivariate predictors of 1-year mortality were analyzed. Overall, 9 patients (6%) experienced major cardiac events postoperatively during their hospitalization...
January 11, 2017: Orthopedics
https://www.readbyqxmd.com/read/28072380/network-functional-connectivity-and-whole-brain-functional-connectomics-to-investigate-cognitive-decline-in-neurodegenerative-conditions
#8
REVIEW
O Dipasquale, Mara Cercignani
Non-invasive mapping of brain functional connectivity (FC) has played a fundamental role in neuroscience, and numerous scientists have been fascinated by its ability to reveal the brain's intricate morphology and functional properties. In recent years, two different techniques have been developed that are able to explore FC in pathophysiological conditions and to provide simple and non-invasive biomarkers for the detection of disease onset, severity and progression. These techniques are independent component analysis, which allows a network-based functional exploration of the brain, and graph theory, which provides a quantitative characterization of the whole-brain FC...
October 2016: Functional Neurology
https://www.readbyqxmd.com/read/28069311/investigating-the-role-of-als-genes-chchd10-and-tuba4a-in-belgian-ftd-als-spectrum-patients
#9
Federica Perrone, Hung Phuoc Nguyen, Sara Van Mossevelde, Matthieu Moisse, Anne Sieben, Patrick Santens, Jan De Bleecker, Mathieu Vandenbulcke, Sebastiaan Engelborghs, Jonathan Baets, Patrick Cras, Rik Vandenberghe, Peter De Jonghe, Peter P De Deyn, Jean-Jacques Martin, Philip Van Damme, Christine Van Broeckhoven, Julie van der Zee
Mutation screening and phenotypic profiling of 2 amyotrophic lateral sclerosis-(ALS) and frontotemporal dementia-(FTD) associated genes, CHCHD10 and TUBA4A, were performed in a Belgian cohort of 459 FTD, 28 FTD-ALS, and 429 ALS patients. In CHCHD10, we identified a novel nonsense mutation (p.Gln108*) in a patient with atypical clinical FTD and pathology-confirmed Parkinson's disease (1/459, 0.22%) leading to loss of transcript. We further observed 3 previously described missense variants (p.Pro34Ser, p.Pro80Leu, and p...
December 21, 2016: Neurobiology of Aging
https://www.readbyqxmd.com/read/28069058/endosulfine-alpha-inhibits-membrane-induced-%C3%AE-synuclein-aggregation-and-protects-against-%C3%AE-synuclein-neurotoxicity
#10
Daniel Ysselstein, Benjamin Dehay, Isabel M Costantino, George P McCabe, Matthew P Frosch, Julia M George, Erwan Bezard, Jean-Christophe Rochet
Neuropathological and genetic findings suggest that the presynaptic protein α-synuclein (aSyn) is involved in the pathogenesis of synucleinopathy disorders, including Parkinson's disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy. Evidence suggests that the self-assembly of aSyn conformers bound to phospholipid membranes in an aggregation-prone state plays a key role in aSyn neurotoxicity. Accordingly, we hypothesized that protein binding partners of lipid-associated aSyn could inhibit the formation of toxic aSyn oligomers at membrane surfaces...
January 10, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28063896/clinical-correlation-of-abnormal-findings-on-magnetic-resonance-elastography-in-idiopathic-normal-pressure-hydrocephalus
#11
Avital Perry, Christopher S Graffeo, Nikoo Fattahi, Mona M ElSheikh, Nealey Cray, Arvin Arani, Richard L Ehman, Kevin J Glaser, Armando Manduca, Fredric B Meyer, John Huston
BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) is ventriculomegaly syndrome characterized by dementia, urinary incontinence, and gait disturbance, which is potentially reversible following ventriculoperitoneal shunting (VPS). Magnetic resonance elastography (MRE) is an evolving imaging technology that noninvasively measures tissue viscoelasticity. OBJECTIVE: We studied iNPH patients using MRE prior to shunting, compared them to normal controls, and analyzed associations between MRE findings and clinical features, as a pilot assessment of MRE in iNPH...
January 4, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28063597/living-near-major-roads-and-the-incidence-of-dementia-parkinson-s-disease-and-multiple-sclerosis-a-population-based-cohort-study
#12
Hong Chen, Jeffrey C Kwong, Ray Copes, Karen Tu, Paul J Villeneuve, Aaron van Donkelaar, Perry Hystad, Randall V Martin, Brian J Murray, Barry Jessiman, Andrew S Wilton, Alexander Kopp, Richard T Burnett
BACKGROUND: Emerging evidence suggests that living near major roads might adversely affect cognition. However, little is known about its relationship with the incidence of dementia, Parkinson's disease, and multiple sclerosis. We aimed to investigate the association between residential proximity to major roadways and the incidence of these three neurological diseases in Ontario, Canada. METHODS: In this population-based cohort study, we assembled two population-based cohorts including all adults aged 20-50 years (about 4·4 million; multiple sclerosis cohort) and all adults aged 55-85 years (about 2·2 million; dementia or Parkinson's disease cohort) who resided in Ontario, Canada on April 1, 2001...
January 4, 2017: Lancet
https://www.readbyqxmd.com/read/28062563/pathology-of-neurodegenerative-diseases
#13
Brittany N Dugger, Dennis W Dickson
Neurodegenerative disorders are characterized by progressive loss of selectively vulnerable populations of neurons, which contrasts with select static neuronal loss because of metabolic or toxic disorders. Neurodegenerative diseases can be classified according to primary clinical features (e.g., dementia, parkinsonism, or motor neuron disease), anatomic distribution of neurodegeneration (e.g., frontotemporal degenerations, extrapyramidal disorders, or spinocerebellar degenerations), or principal molecular abnormality...
January 6, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28061383/increased-blood-brain-barrier-permeability-is-associated-with-dementia-and-diabetes-but-not-amyloid-pathology-or-apoe-genotype
#14
Shorena Janelidze, Joakim Hertze, Katarina Nägga, Karin Nilsson, Christer Nilsson, Malin Wennström, Danielle van Westen, Kaj Blennow, Henrik Zetterberg, Oskar Hansson
Blood-brain barrier (BBB) dysfunction might be an important component of many neurodegenerative disorders. In this study, we investigated its role in dementia using large clinical cohorts. The cerebrospinal fluid (CSF)/plasma albumin ratio (Qalb), an indicator of BBB (and blood-CSF barrier) permeability, was measured in a total of 1015 individuals. The ratio was increased in patients with Alzheimer's disease, dementia with Lewy bodies or Parkinson's disease dementia, subcortical vascular dementia, and frontotemporal dementia compared with controls...
December 5, 2016: Neurobiology of Aging
https://www.readbyqxmd.com/read/28059471/specific-patterns-of-neuronal-loss-in-the-pulvinar-nucleus-in-dementia-with-lewy-bodies
#15
Daniel Erskine, Alan J Thomas, Johannes Attems, John-Paul Taylor, Ian G McKeith, Christopher M Morris, Ahmad A Khundakar
BACKGROUND: Complex visual hallucinations occur in 70%-80% of dementia with Lewy bodies patients and significantly affect well-being. Despite the prevalence of visual hallucinations in dementia with Lewy bodies, the neuropathological basis of this phenomenon is poorly understood. The pulvinar nucleus of the thalamus has not previously been neuropathologically examined, but has been linked to visual hallucinations in dementia with Lewy bodies. The objective of this study was to investigate whether neuropathological or morphometric changes occur in the pulvinar nucleus in dementia with Lewy bodies cases that may contribute to visual hallucinations...
January 6, 2017: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/28050656/the-recommendations-of-a-consensus-panel-for-the-screening-diagnosis-and-treatment-of-neurogenic-orthostatic-hypotension-and-associated-supine-hypertension
#16
REVIEW
Christopher H Gibbons, Peter Schmidt, Italo Biaggioni, Camille Frazier-Mills, Roy Freeman, Stuart Isaacson, Beverly Karabin, Louis Kuritzky, Mark Lew, Phillip Low, Ali Mehdirad, Satish R Raj, Steven Vernino, Horacio Kaufmann
Neurogenic orthostatic hypotension (nOH) is common in patients with neurodegenerative disorders such as Parkinson's disease, multiple system atrophy, pure autonomic failure, dementia with Lewy bodies, and peripheral neuropathies including amyloid or diabetic neuropathy. Due to the frequency of nOH in the aging population, clinicians need to be well informed about its diagnosis and management. To date, studies of nOH have used different outcome measures and various methods of diagnosis, thereby preventing the generation of evidence-based guidelines to direct clinicians towards 'best practices' when treating patients with nOH and associated supine hypertension...
January 3, 2017: Journal of Neurology
https://www.readbyqxmd.com/read/28044062/opening-up-the-dna-methylome-of-dementia
#17
R Delgado-Morales, M Esteller
Dementia is a complex clinical condition characterized by several cognitive impairments that interfere with patient independence in executing everyday tasks. Various neurodegenerative disorders have dementia in common among their clinical manifestations. In addition, these diseases, such as Alzheimer's disease, Parkinson's disease, dementia with Lewy bodies and frontotemporal dementia, share molecular alterations at the neuropathological level. In recent years, the field of neuroepigenetics has expanded massively and it is now clear that epigenetic processes, such as DNA methylation, are mechanisms involved in both normal and pathological brain function...
January 3, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28042767/advantages-of-structure-based-drug-design-approaches-in-neurological-disorders
#18
Murali Aarthy, Umesh Panwar, Chandrabose Selvaraj, Sanjeev Kumar Singh
The nerve impulse that function during abnormal or due in illness may due to several genetic factors, metabolic, biological conditions or environmental components denominated as Neuro-biological disorders. This illness occurs mostly due to the innumerable biological modifications that alters the mechanistic condition of the brain. As per current update, more than a millions of people around the world are suffering through various kinds of neurological disorders. In case, 50 million people with Epilepsy, 35 million with dementia, mainly included Alzheimer's disease and the rest of other cases with Parkinson's, Migraine and Stroke...
2, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28031997/cortical-asymmetry-in-parkinson-s-disease-early-susceptibility-of-the-left-hemisphere
#19
Daniel O Claassen, Katherine E McDonell, Manus Donahue, Shiv Rawal, Scott A Wylie, Joseph S Neimat, Hakmook Kang, Peter Hedera, David Zald, Bennett Landman, Benoit Dawant, Swati Rane
BACKGROUND AND PURPOSE: Clinically, Parkinson's disease (PD) presents with asymmetric motor symptoms. The left nigrostriatal system appears more susceptible to early degeneration than the right, and a left-lateralized pattern of early neuropathological changes is also described in several neurodegenerative conditions, including Alzheimer's disease, frontotemporal dementia, and Huntington's disease. In this study, we evaluated hemispheric differences in estimated rates of atrophy in a large, well-characterized cohort of PD patients...
December 2016: Brain and Behavior
https://www.readbyqxmd.com/read/28028735/mapping-of-surface-exposed-epitopes-of-in-vitro-and-in-vivo-aggregated-species-of-alpha-synuclein
#20
Leire Almandoz-Gil, Veronica Lindström, Jessica Sigvardson, Philipp J Kahle, Lars Lannfelt, Martin Ingelsson, Joakim Bergström
Aggregated alpha-synuclein is the main component of Lewy bodies, intraneuronal deposits observed in Parkinson's disease and dementia with Lewy bodies. The objective of the study was to identify surface-exposed epitopes of alpha-synuclein in vitro and in vivo formed aggregates. Polyclonal immunoglobulin Y antibodies were raised against short linear peptides of the alpha-synuclein molecule. An epitope in the N-terminal region (1-10) and all C-terminal epitopes (90-140) were found to be exposed in an indirect enzyme-linked immunosorbent assay (ELISA) using recombinant monomeric, oligomeric, and fibrillar alpha-synuclein...
December 27, 2016: Cellular and Molecular Neurobiology
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