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https://www.readbyqxmd.com/read/29236052/micrornas-in-parkinson-s-disease-from-pathogenesis-to-novel-diagnostic-and-therapeutic-approaches
#1
REVIEW
Loredana Leggio, Silvia Vivarelli, Francesca L'Episcopo, Cataldo Tirolo, Salvo Caniglia, Nunzio Testa, Bianca Marchetti, Nunzio Iraci
Parkinson's disease (PD) is the most prevalent central nervous system (CNS) movement disorder and the second most common neurodegenerative disease overall. PD is characterized by the progressive loss of dopaminergic (DAergic) neurons in the substantia nigra pars compacta (SNpc) within the midbrain, accumulation of alpha-synuclein (α-SYN) in Lewy bodies and neurites and excessive neuroinflammation. The neurodegenerative processes typically begin decades before the appearance of clinical symptoms. Therefore, the diagnosis is achievable only when the majority of the relevant DAergic neurons have already died and for that reason available treatments are only palliative at best...
December 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29234177/the-effects-of-piper-guineense-versus-sesamum-indicum-aqueous-extracts-on-lipid-metabolism-and-antioxidants-in-hypercholesterolemic-rats
#2
Sarah O Nwozo, Yetunde T Lewis, Babatunji E Oyinloye
Background: Piper guineense (PG) and Sesamum indicum (SI) have been shown to be rich sources of antioxidants and other health benefits; hence, we evaluated the impact of its consumption in hypercholesterolemic model on lipid metabolism. Methods: Forty-eight animals were divided into eight groups of six rats each. Rats were given cholesterol (40 mg/0.3ml), PG and SI extract (100 and 200 mg/kg), and Questran (0.26 g/kg) orally, five times a week for 28 days. Lipid profile, hepatic antioxidant status, biomarkers of liver toxicity, and tissue histopathology were examined...
September 2017: Iranian Journal of Medical Sciences
https://www.readbyqxmd.com/read/29233218/secondary-nucleation-of-monomers-on-fibril-surface-dominates-%C3%AE-synuclein-aggregation-and-provides-autocatalytic-amyloid-amplification
#3
Ricardo Gaspar, Georg Meisl, Alexander K Buell, Laurence Young, Clemens F Kaminski, Tuomas P J Knowles, Emma Sparr, Sara Linse
Parkinson's disease (PD) is characterized by proteinaceous aggregates named Lewy Bodies and Lewy Neurites containing α-synuclein fibrils. The underlying aggregation mechanism of this protein is dominated by a secondary process at mildly acidic pH, as in endosomes and other organelles. This effect manifests as a strong acceleration of the aggregation in the presence of seeds and a weak dependence of the aggregation rate on monomer concentration. The molecular mechanism underlying this process could be nucleation of monomers on fibril surfaces or fibril fragmentation...
January 2017: Quarterly Reviews of Biophysics
https://www.readbyqxmd.com/read/29232244/-occipital-tunnel-sign-on-fdg-pet-for-differentiating-dementias
#4
David M Sawyer, Phillip H Kuo
PET using FDG is a critical tool for evaluation of dementias, with characteristic patterns of hypometabolism suggesting specific diagnoses. Hypometabolism in the occipital region is recognized as an important finding associated with dementia with Lewy bodies and posterior cortical atrophy. We describe here the novel "occipital tunnel" sign, which results from relative sparing of FDG uptake in the medial occipital (primary visual) cortex compared with more severe loss in the surrounding lateral occipital (visual association) cortex...
December 11, 2017: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/29228071/associations-between-tau-%C3%AE-amyloid-and-cognition-in-parkinson-disease
#5
Joseph R Winer, Anne Maass, Peter Pressman, Jordan Stiver, Daniel R Schonhaut, Suzanne L Baker, Joel Kramer, Gil D Rabinovici, William J Jagust
Importance: Multiple disease processes are associated with cognitive impairment in Parkinson disease (PD), including Lewy bodies, cerebrovascular disease, and Alzheimer disease. It remains unknown whether tau pathology relates to cognition in patients with PD without dementia. Objective: To compare tau aggregation in patients with PD who are cognitively normal (PD-CN), patients with PD with mild cognitive impairment (PD-MCI), and healthy control participants, and evaluate the relationships between β-amyloid (Aβ), tau, and cognition in patients with PD who did not have dementia...
December 11, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/29223171/caregiver-burden-sleep-quality-depression-and-anxiety-in-dementia-caregivers-a-comparison-of-frontotemporal-lobar-degeneration-dementia-with-lewy-bodies-and-alzheimer-s-disease
#6
Shuai Liu, Jing Liu, Xiao-Dan Wang, Zhihong Shi, Yuying Zhou, Jing Li, Tao Yu, Yong Ji
BACKGROUND: Very few recent studies are available that compare caregiver burden, sleep quality, and stress in caregivers of different types of dementia. We aimed to investigate caregiver burden, sleep quality, and stress in caregivers of patients with frontotemporal lobar degeneration and dementia with Lewy bodies, as compared with caregivers of patients with Alzheimer's disease. METHODS: This study was carried out from March 2011 to January 2014. In total, 492 dyads of patient and caregiver (frontotemporal lobar degeneration, n = 131; dementia with Lewy bodies, n = 36; Alzheimer's disease, n = 325) participated in this study...
December 10, 2017: International Psychogeriatrics
https://www.readbyqxmd.com/read/29222591/dementia-with-lewy-bodies-and-parkinson-s-disease-dementia-current-concepts-and-controversies
#7
REVIEW
Kurt A Jellinger
Dementia with Lewy bodies (DLB) and Parkinson's disease-dementia (PDD), although sharing many clinical, neurochemical and morphological features, according to DSM-5, are two entities of major neurocognitive disorders with Lewy bodies of unknown etiology. Despite considerable clinical overlap, their diagnosis is based on an arbitrary distinction between the time of onset of motor and cognitive symptoms: dementia often preceding parkinsonism in DLB and onset of cognitive impairment after onset of motor symptoms in PDD...
December 8, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/29221458/a-cohort-examination-to-establish-reporting-of-the-remit-and-function-of-trial-steering-committees-in-randomised-controlled-trials
#8
Elizabeth J Conroy, Barbara Arch, Nicola L Harman, J Athene Lane, Steff C Lewis, John Norrie, Matthew R Sydes, Carrol Gamble
BACKGROUND: The DAMOCLES project established a widely used Data Monitoring Committee (DMC) Charter for randomised controlled trials (RCTs). Typically, within the UK, the DMC is advisory and recommends to another executive body; the Trial Steering Committee (TSC). Despite the executive role of the TSC, the CONSORT Statement does not explicitly require reporting of TSC activity, although is included as an example of good reporting. A lack of guidance on TSC reporting can impact transparency of trial oversight, ultimately leading to a misunderstanding regarding role and, subsequently, further variation in practice...
December 8, 2017: Trials
https://www.readbyqxmd.com/read/29218503/differential-alterations-in-metabolism-and-proteolysis-related-proteins-in-human-parkinson-s-disease-substantia-nigra
#9
Edna Grünblatt, Josefine Ruder, Camelia Maria Monoranu, Peter Riederer, Moussa Bh Youdim, Silvia A Mandel
Parkinson's disease is the most common neurodegenerative disorder after Alzheimer's disease, with the majority of cases being sporadic or "idiopathic". The aetiology of the sporadic form is still unknown, but there is a broad consensus that Parkinson's disease involves multiple pathways. In previous human post-mortem studies investigating substantia nigra of parkinsonian subjects, gene expression alterations in various metabolic pathways including protein folding, trafficking, aggregation, ubiquitination and oxidative stress were found...
December 7, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/29217406/lncrna-snhg1-promotes-%C3%AE-synuclein-aggregation-and-toxicity-by-targeting-mir-15b-5p-to-activate-siah1-in-human-neuroblastoma-sh-sy5y-cells
#10
Yuan Chen, Ya-Jun Lian, Yun-Qing Ma, Chuan-Jie Wu, Ya-Ke Zheng, Nan-Chang Xie
Numerous long non-coding RNAs (lncRNAs) have been identified as aberrantly expressed in Parkinson's disease (PD). However, limited knowledge is available concerning the roles of dysregulated lncRNAs and the underlying molecular regulatory mechanism in the pathological process of PD. In this study, we found that lncRNA small nucleolar RNA host gene 1 (SNHG1) and seven in absentia homolog 1 (SIAH1) were upregulated, but microRNA-15b-5p (miR-15b-5p) was downregulated in SH-SY5Y cells pretreated with MPP+, as well as in MPTP-induced mouse model of PD...
December 4, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/29216908/clinical-and-neuropathological-features-of-als-ftd-with-tia1-mutations
#11
Veronica Hirsch-Reinshagen, Cyril Pottier, Alexandra M Nicholson, Matt Baker, Ging-Yuek R Hsiung, Charles Krieger, Pheth Sengdy, Kevin B Boylan, Dennis W Dickson, Marsel Mesulam, Sandra Weintraub, Eileen Bigio, Lorne Zinman, Julia Keith, Ekaterina Rogaeva, Sasha A Zivkovic, David Lacomis, J Paul Taylor, Rosa Rademakers, Ian R A Mackenzie
Mutations in the stress granule protein T-cell restricted intracellular antigen 1 (TIA1) were recently shown to cause amyotrophic lateral sclerosis (ALS) with or without frontotemporal dementia (FTD). Here, we provide detailed clinical and neuropathological descriptions of nine cases with TIA1 mutations, together with comparisons to sporadic ALS (sALS) and ALS due to repeat expansions in C9orf72 (C9orf72+). All nine patients with confirmed mutations in TIA1 were female. The clinical phenotype was heterogeneous with a range in the age at onset from late twenties to the eighth decade (mean = 60 years) and disease duration from one to 6 years (mean = 3 years)...
December 7, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/29215750/questionnaire-based-problematic-relationship-to-eating-and-food-is-associated-with-25-year-body-mass-index-trajectories-during-midlife-the-coronary-artery-risk-development-in-young-adults-cardia-study
#12
Cynthia Yoon, David R Jacobs, Daniel A Duprez, Gareth Dutton, Cora E Lewis, Dianne Neumark-Sztainer, Lyn M Steffen, Delia S West, Susan M Mason
OBJECTIVE: Problematic eating behaviors and attitudes are of public health concern. Questionnaire-based assessment of these behaviors is important for large-scale research on eating behaviors. The questionnaire on eating and weight patterns-revised (QEWP-R) measures potential problematic behaviors and attitudes toward food (including anxieties, compensatory actions, overeating and loss of control, dieting, and shape concerns) that in aggregate may indicate diagnosable eating disorders...
December 7, 2017: International Journal of Eating Disorders
https://www.readbyqxmd.com/read/29213511/lewy-and-his-inclusion-bodies-discovery-and-rejection
#13
Eliasz Engelhardt, Marleide da Mota Gomes
Fritz Jacob Heinrich Lewy described the pathology of Paralysis agitans [Parkinson disease] and was the first to identify eosinophilic inclusion bodies in neurons of certain brain nuclei, later known as Lewy bodies, the pathological signature of the Lewy body diseases. In 1912, he published his seminal study, followed soon after by an update paper, and 10 years later, in 1923, by his voluminous book, where he exhaustively described the subject. The publication provided extensive information on the pathology of Paralysis agitans, and the entirely novel finding of eosinophilic inclusion bodies, which would become widely recognized and debated in the future...
April 2017: Dementia & Neuropsychologia
https://www.readbyqxmd.com/read/29208076/improving-diagnostic-communication-in-dementia
#14
Sheung-Tak Cheng, Linda C W Lam
In many countries around the world, owing to the lack of specialists and equipment, delay up to a few years in help-seeking and getting diagnostic examinations for dementia is not uncommon (Sayegh and Knight, 2013), and this situation is considerably more serious in "atypical dementias" due to the challenge they present for differential diagnosis. For instance, a survey in the USA showed that misdiagnosis was common in patients with Lewy body dementia who, on average, saw at least three physicians over a year's time or more before getting the proper diagnosis (Lewy Body Dementia Association, 2010)...
December 6, 2017: International Psychogeriatrics
https://www.readbyqxmd.com/read/29204520/comprehensive-assessment-of-circulating-immune-cell-populations-in-response-to-stereotactic-body-radiation-therapy-in-patients-with-liver-cancer
#15
Michael P Gustafson, Svetlana Bornschlegl, Sean S Park, Dennis A Gastineau, Lewis R Roberts, Allan B Dietz, Christopher L Hallemeier
Stereotactic body radiation therapy (SBRT) can positively influence an antitumor immune response by inducing necrotic cell death. SBRT also been shown to eliminate tumors outside the radiation therapy field through an immune-mediated process known as the abscopal effect. Recent advances in immunotherapy may provide new therapeutic approaches for patients with liver cancer. Therefore, understanding the immune status of patients with cancer will likely guide how immunotherapy might be used in combination with SBRT...
October 2017: Advances in Radiation Oncology
https://www.readbyqxmd.com/read/29198208/association-between-childhood-infection-serum-inflammatory-markers-and-intelligence-findings-from-a-population-based-prospective-birth-cohort-study
#16
N Mackinnon, S Zammit, G Lewis, P B Jones, G M Khandaker
A link between infection, inflammation, neurodevelopment and adult illnesses has been proposed. The objective of this study was to examine the association between infection burden during childhood - a critical period of development for the immune and nervous systems - and subsequent systemic inflammatory markers and general intelligence. In the Avon Longitudinal Study of Parents and Children, a prospective birth cohort in England, we examined the association of exposure to infections during childhood, assessed at seven follow-ups between age 1·5 and 7·5 years, with subsequent: (1) serum interleukin 6 and C-reactive protein (CRP) levels at age 9; (2) intelligence quotient (IQ) at age 8...
December 4, 2017: Epidemiology and Infection
https://www.readbyqxmd.com/read/29198173/autophagy-inhibition-promotes-snca-alpha-synuclein-release-and-transfer-via-extracellular-vesicles-with-a-hybrid-autophagosome-exosome-like-phenotype
#17
Georgia Minakaki, Stefanie Menges, Agnes Kittel, Evangelia Emmanouilidou, Iris Schaeffner, Katalin Barkovits, Anna Bergmann, Edward Rockenstein, Anthony Adame, Franz Marxreiter, Brit Mollenhauer, Douglas Galasko, Edit Irén Buzás, Ursula Schlötzer-Schrehardt, Katrin Marcus, Wei Xiang, Dieter Chichung Lie, Kostas Vekrellis, Eliezer Masliah, Jürgen Winkler, Jochen Klucken
The autophagy-lysosome pathway (ALP) regulates intracellular homeostasis of the cytosolic protein SNCA/alpha-synuclein and is impaired in synucleinopathies, including Parkinson disease and dementia with Lewy bodies (DLB). Emerging evidence suggests that ALP influences SNCA release, but the underlying cellular mechanisms are not well understood. Several studies identified SNCA in exosome/extracellular vesicle (EV) fractions. EVs are generated in the multivesicular body compartment and either released upon its fusion with the plasma membrane, or cleared via the ALP...
December 4, 2017: Autophagy
https://www.readbyqxmd.com/read/29197507/association-between-a-functional-interleukin-6-receptor-genetic-variant-and-risk-of-depression-and-psychosis-in-a-population-based-birth-cohort
#18
Golam M Khandaker, Stanley Zammit, Stephen Burgess, Glyn Lewis, Peter B Jones
OBJECTIVE: Interleukin 6 (IL-6) levels are commonly elevated in patients with depression and psychosis and in people who are at risk of developing these disorders. A common, functional variant in the IL6R gene (IL6R Asp358Ala; rs2228145 A > C) is known to dampen down inflammation by impairing IL6R signaling. We have examined the association of Asp358Ala with diagnosis of depression and psychosis, serum IL-6, CRP levels, and a number of risk factors commonly linked with inflammation, depression or psychosis...
December 2, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29196808/propagation-of-alpha-synuclein-pathology-from-the-olfactory-bulb-possible-role-in-the-pathogenesis-of-dementia-with-lewy-bodies
#19
REVIEW
María Graciela Cersosimo
Olfactory limbic structures, like the amygdala, the entorhinal, and the piriform cortices, are closely involved in cognitive processes. Thus, besides olfactory dysfunctions, it is conceivable that the compromise of these structures can lead to cognitive impairment. The olfactory bulb is affected by alpha-synuclein pathology in almost all cases of both Parkinson's disease and dementia with Lewy bodies. The clinical distinction between these disorders relies on the timing in the appearance of dementia in relationship to motor symptoms...
December 1, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/29196214/the-lysosomal-enzyme-alpha-galactosidase-a-is-deficient-in-parkinson-s-disease-brain-in-association-with-the-pathologic-accumulation-of-alpha-synuclein
#20
Michael P Nelson, Michel Boutin, Tonia E Tse, Hailin Lu, Emily D Haley, Xiaosen Ouyang, Jianhua Zhang, Christiane Auray-Blais, John J Shacka
The aberrant accumulation of alpha-synuclein (α-syn) is believed to contribute to the onset and pathogenesis of Parkinson's disease (PD). The autophagy-lysosome pathway (ALP) is responsible for the high capacity clearance of α-syn. ALP dysfunction is documented in PD and pre-clinical evidence suggests that inhibiting the ALP promotes the pathological accumulation of α-syn. We previously identified the pathological accumulation of α-syn in the brains of mice deficient for the soluble lysosomal enzyme alpha-Galactosidase A (α-Gal A), a member of the glycosphingolipid metabolism pathway...
December 2, 2017: Neurobiology of Disease
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