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https://www.readbyqxmd.com/read/27914298/effects-of-environmental-noise-exposure-on-dna-methylation-in-the-brain-and-metabolic-health
#1
Liqiong Guo, Peng-Hui Li, Hua Li, Elena Colicino, Silvia Colicino, Yi Wen, Ruiping Zhang, Xiaotian Feng, Timothy M Barrow, Akin Cayir, Andrea A Baccarelli, Hyang-Min Byun
Environmental noise exposure is associated with adverse effects on human health including hearing loss, heart disease, and changes in stress-related hormone levels. Alteration in DNA methylation in response to environmental exposures is a well-known phenomenon and it is implicated in many human diseases. Understanding how environmental noise exposures affect DNA methylation patterns may help to elucidate the link between noise and adverse effects on health. In this pilot study we examined the effects of environmental noise exposure on DNA methylation of genes related to brain function and investigated whether these changes are related with metabolic health...
November 30, 2016: Environmental Research
https://www.readbyqxmd.com/read/27818248/genetics-of-parkinson-s-disease
#2
REVIEW
Christina M Lill
Almost two decades after the identification of SNCA as the first causative gene in Parkinson's disease (PD) and the subsequent understanding that genetic factors play a substantial role in PD development, our knowledge of the genetic architecture underlying this disease has vastly improved. Approximately 5-10% of patients suffer from a monogenic form of PD where autosomal dominant mutations in SNCA, LRRK2, and VPS35 and autosomal recessive mutations in PINK1, DJ-1, and Parkin cause the disease with high penetrance...
December 2016: Molecular and Cellular Probes
https://www.readbyqxmd.com/read/27777137/autosomal-dominant-parkinson-s-disease-incidence-of-mutations-in-lrrk2-snca-vps35-and-gba-genes-in-brazil
#3
Gabriella de M Abreu, Débora Cristina T Valença, Mário Campos, Camilla P da Silva, João S Pereira, Marco A Araujo Leite, Ana Lucia Rosso, Denise H Nicaretta, Luiz Felipe R Vasconcellos, Delson José da Silva, Marcus V Della Coletta, Jussara M Dos Santos, Andressa P Gonçalves, Cíntia B Santos-Rebouças, Márcia M G Pimentel
INTRODUCTION: Amongst Parkinson's disease (PD) genetic factors, mutations in LRRK2, SNCA, VPS35 and GBA genes are recognized causes of PD. Nonetheless, few genetic screenings have been conducted in families with a history of PD consistent with autosomal dominant inheritance (ADPD), and their relevance to the etiology of PD has been poorly explored in Latin American populations, such as the Brazilian one, with a high degree of admixture. METHODS: In order to assess the contribution of specific mutations in LRRK2, SNCA, VPS35 and GBA genes to ADPD in Brazil, we conducted the first molecular evaluation in a cohort of 141 index cases from families with ADPD...
December 2, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/27759945/dna-methylation-and-alcohol-use-disorders-progress-and-challenges
#4
Huiping Zhang, Joel Gelernter
BACKGROUND AND OBJECTIVES: Risk for alcohol use disorders (AUDs) is influenced by gene-environment interactions. Environmental factors can affect gene expression through epigenetic mechanisms such as DNA methylation. This review outlines the findings regarding the association of DNA methylation and AUDs. METHODS: We searched PubMed (by April 2016) and identified 29 studies that examined the association of DNA methylation and AUDs. We also evaluated the methods used in these studies...
October 19, 2016: American Journal on Addictions
https://www.readbyqxmd.com/read/27757834/transcriptome-profile-changes-in-mice-with-mptp-induced-early-stages-of-parkinson-s-disease
#5
Anelya Kh Alieva, Elena V Filatova, Anna A Kolacheva, Margarita M Rudenok, Petr A Slominsky, Mikhail V Ugrumov, Maria I Shadrina
Parkinson's disease (PD) is one of the most common neurodegenerative diseases. Despite progress in the study of the molecular, genetic, and pathogenic mechanisms of PD, it is unclear which processes trigger the development of the pathology associated with PD. Models of the presymptomatic and early symptomatic stages of PD induced by MPTP have been used to analyze changes in transcriptome profile in brain tissues, to identify specific patterns and mechanisms underlying neurodegeneration in PD. The whole-transcriptome analysis in the brain tissues of the mice with MPTP-induced PD showed that striatum is involved in the pathogenesis in the earliest stages and the processes associated with vesicular transport may be altered...
October 18, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27745782/association-between-common-genetic-risk-variants-and-depression-in-parkinson-s-disease-a-dpd-study-in-chinese
#6
Xiaojuan Dan, Chaodong Wang, Jinglin Zhang, Zhuqin Gu, Yongtao Zhou, Jinghong Ma, Piu Chan
INTRODUCTION: Prediction of depression in patients with Parkinson's disease (PD) remains challenging. We investigated whether the common susceptible genetic variants for PD are associated with the risk and improves prediction of development of depression in PD (dPD). METHODS: 1134 individuals with a primary diagnosis of PD were recruited. Demographic information, Unified Parkinson's Disease Rating Scale (UPDRS), and 17-item Hamilton Rating Scale for Depression (HAMD) were obtained...
September 29, 2016: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/27743341/finding-the-guilty-gene-variant-of-sporadic-parkinson-s-disease-via-crispr-cas9
#7
Shenzhao Lu, Jiawei Zhou
Parkinson's disease (PD) is a common neurodegenerative disorder affecting millions of people worldwide, but its cause and pathogenesis are still not fully understood. Earlier studies have shown that SNCA, which encodes α-synuclein, is one of the key genes associated with PD. Single-nucleotide polymorphism (SNP) variants of SNCA are thought to be correlated with disease onset. The underlying mechanisms however are enigmatic. A recent study published in Nature revealed that one of the SNP variants in the SNCA non-coding element elevated α-synuclein expression in human neurons by reducing the binding efficiency of transcription factors, demonstrating a previously uncharted role for SNPs in the pathogenesis of PD...
October 14, 2016: Neuroscience Bulletin
https://www.readbyqxmd.com/read/27717584/parkinson-s-disease-snca-park2-and-lrrk2-targeting-micrornas-elevated-in-cingulate-gyrus
#8
Roman Tatura, Theo Kraus, Armin Giese, Thomas Arzberger, Malte Buchholz, Günter Höglinger, Ulrich Müller
INTRODUCTION: In order to better understand the role of epigenetic influences in the etiology of Parkinson's disease (PD), we studied the expression of microRNAs in gyri cinguli of patients and controls. METHODS: Expression profiling of 744 well-characterized microRNAs in gyri cinguli from patients and controls using TaqMan array microRNA cards. Verification of significantly dysregulated microRNAs by SYBR Green qRT-PCR. RESULTS: First screen by TaqMan array identified 43 microRNAs that were upregulated in gyri cinguli from patients...
September 28, 2016: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/27704156/oxidative-stress-and-gene-expression-profiling-of-cell-death-pathways-in-alpha-cypermethrin-treated-sh-sy5y-cells
#9
Alejandro Romero, Eva Ramos, Irma Ares, Víctor Castellano, Marta Martínez, María-Rosa Martínez-Larrañaga, Arturo Anadón, María-Aránzazu Martínez
In this study, we investigated the induction of oxidative stress and apoptosis in human neuroblastoma cell line SH-SY5Y in response to alpha-cypermethrin (α-CYPER) exposure. MTT and LDH assays were carried out to assess the α-CYPER cytotoxicity. The IC50 value for α-CYPER was calculated to be 78.3 ± 2.98 µM for the MTT assay and 71.5 ± 3.94 µM for LDH assay. The pyrethroid α-CYPER (1-100 µM), in a dose-dependent manner, induced a significant increase in lipid peroxides measured as malondialdehyde (MDA) and in the levels of nitric oxide (NO)...
October 4, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27699750/-frequency-of-single-nucleotide-polymorphisms-and-alpha-synuclein-haplotypes-associated-with-sporadic-parkinson-s-disease-in-the-mexican-population
#10
D J Davila-Ortiz de Montellano, M Rodriguez-Violante, A Fresan, N Monroy-Jaramillo, P Yescas-Gomez
INTRODUCTION: Parkinson's disease (PD) is a common neurodegenerative disease which begins in adulthood. Its incidence in Mexico is estimated to be 40-50 cases per 100,000 inhabitants/year and is the fourth reason for medical care in the National Institute of Neurology and Neurosurgery. The protein alpha-synuclein, SNCA, plays a key role in the pathology of PD, and its polymorphisms have been associated with an increased risk of developing the disease. AIM: To evaluate the risk of PD represented by the polymorphisms rs2619364, rs2619363, rs2736990, rs7684318, rs17016074, rs356219, rs356220 and rs356203 of SNCA in a sample of Mexican subjects...
October 16, 2016: Revista de Neurologia
https://www.readbyqxmd.com/read/27697694/regional-expression-of-the-mapt-gene-is-associated-with-loss-of-hubs-in-brain-networks-and-cognitive-impairment-in-parkinson-disease-and-progressive-supranuclear-palsy
#11
Timothy Rittman, Mikail Rubinov, Petra E Vértes, Ameera X Patel, Cedric E Ginestet, Boyd C P Ghosh, Roger A Barker, Maria Grazia Spillantini, Edward T Bullmore, James B Rowe
Abnormalities of tau protein are central to the pathogenesis of progressive supranuclear palsy, whereas haplotype variation of the tau gene MAPT influences the risk of Parkinson disease and Parkinson's disease dementia. We assessed whether regional MAPT expression might be associated with selective vulnerability of global brain networks to neurodegenerative pathology. Using task-free functional magnetic resonance imaging in progressive supranuclear palsy, Parkinson disease, and healthy subjects (n = 128), we examined functional brain networks and measured the connection strength between 471 gray matter regions...
September 9, 2016: Neurobiology of Aging
https://www.readbyqxmd.com/read/27685250/dna-methylation-changes-at-snca-intron-1-in-patients-with-dementia-with-lewy-bodies
#12
Yu Funahashi, Yuta Yoshino, Kiyohiro Yamazaki, Yoko Mori, Takaaki Mori, Yuki Ozaki, Tomoko Sao, Shinichiro Ochi, Jun-Ichi Iga, Shu-Ichi Ueno
AIM: It is difficult to diagnose dementia with Lewy bodies (DLB) because it exhibits clinical and neuropathological overlap with both Alzheimer's disease and Parkinson's disease. The α-synuclein protein is a major component of Lewy bodies, and accumulation of α-synuclein aggregates causes synaptic dysfunction in DLB. Epigenetic changes at the synuclein alpha ( SNCA ) gene may be involved in DLB pathogenesis. METHODS: We examined DNA methylation rates at 10 CpG sites located in intron 1 of SNCA and SNCA mRNA expression in peripheral leukocytes to compare DLB patients (n = 20; nine men, 11 women; age = 78...
September 29, 2016: Psychiatry and Clinical Neurosciences
https://www.readbyqxmd.com/read/27668119/analysis-of-lrrk2-snca-and-itga8-gene-variants-with-sporadic-parkinson-s-disease-susceptibility-in-chinese-han-population
#13
Jie Fang, Kehui Yi, Mingwei Guo, Xingkai An, Hongli Qu, Qing Lin, Min Bi, Qilin Ma
Background. Parkinson's disease (PD) is an age-related neurodegenerative disease affected by multiple genetic and environmental factors. We performed a case-control study on candidate gene to scrutinize whether genetic variants in LRRK2, SNCA, and ITGA8 genes could be associated with sporadic PD in Chinese Han population. Methods. Five single-nucleotide polymorphisms (SNPs) of LRRK2 (rs1491942), SNCA (rs2301134, rs2301135, and rs356221), and ITGA8 (rs7077361) were selected and genotyped among 583 unrelated PD patients and 558 healthy controls...
2016: Parkinson's Disease
https://www.readbyqxmd.com/read/27631132/alpha-synuclein-a-novel-viral-restriction-factor-hiding-in-plain-sight
#14
Aaron R Massey, J David Beckham
Alpha-synuclein (α-syn) is a highly conserved protein encoded by the SNCA gene and is expressed uniquely in neurons of both the central and peripheral nervous systems (CNS and PNS). α-Syn is known to cause sporadic and familial forms of Parkinson's disease (PD). However, the role for neuronal expression of α-syn in the first place remains unknown. We review and discuss recently published work that suggests a novel role for α-syn expression in neurons as a restriction factor that inhibits virus transmission from the PNS to the CNS...
September 15, 2016: DNA and Cell Biology
https://www.readbyqxmd.com/read/27629089/a-genome-wide-association-study-in-multiple-system-atrophy
#15
Anna Sailer, Sonja W Scholz, Michael A Nalls, Claudia Schulte, Monica Federoff, T Ryan Price, Andrew Lees, Owen A Ross, Dennis W Dickson, Kin Mok, Niccolo E Mencacci, Lucia Schottlaender, Viorica Chelban, Helen Ling, Sean S O'Sullivan, Nicholas W Wood, Bryan J Traynor, Luigi Ferrucci, Howard J Federoff, Timothy R Mhyre, Huw R Morris, Günther Deuschl, Niall Quinn, Hakan Widner, Alberto Albanese, Jon Infante, Kailash P Bhatia, Werner Poewe, Wolfgang Oertel, Günter U Höglinger, Ullrich Wüllner, Stefano Goldwurm, Maria Teresa Pellecchia, Joaquim Ferreira, Eduardo Tolosa, Bastiaan R Bloem, Olivier Rascol, Wassilios G Meissner, John A Hardy, Tamas Revesz, Janice L Holton, Thomas Gasser, Gregor K Wenning, Andrew B Singleton, Henry Houlden
OBJECTIVE: To identify genetic variants that play a role in the pathogenesis of multiple system atrophy (MSA), we undertook a genome-wide association study (GWAS). METHODS: We performed a GWAS with >5 million genotyped and imputed single nucleotide polymorphisms (SNPs) in 918 patients with MSA of European ancestry and 3,864 controls. MSA cases were collected from North American and European centers, one third of which were neuropathologically confirmed. RESULTS: We found no significant loci after stringent multiple testing correction...
October 11, 2016: Neurology
https://www.readbyqxmd.com/read/27613618/disease-toxicant-interactions-in-parkinson-s-disease-neuropathology
#16
Gunnar F Kwakye, Rachael A McMinimy, Michael Aschner
Human disease commonly manifests as a result of complex genetic and environmental interactions. In the case of neurodegenerative diseases, such as Parkinson's disease (PD), understanding how environmental exposures collude with genetic polymorphisms in the central nervous system to cause dysfunction is critical in order to develop better treatment strategies, therapies, and a more cohesive paradigm for future research. The intersection of genetics and the environment in disease etiology is particularly relevant in the context of their shared pathophysiological mechanisms...
September 9, 2016: Neurochemical Research
https://www.readbyqxmd.com/read/27613114/genetic-causes-of-parkinson-s-disease-in-the-maltese-a-study-of-selected-mutations-in-lrrk2-mthfr-qdpr-and-spr
#17
Charmaine Zahra, Christine Tabone, Graziella Camilleri, Alex E Felice, Rosienne Farrugia, Stephanie Bezzina Wettinger
BACKGROUND: Mutations in Leucine-rich repeat kinase 2 NM_198578 (LRRK2 c.6055G > A (p.G2019S), LRRK2 c.4321C > G (p.R1441G)) and alpha-synuclein NM_000345 (SNCA c.209G > A (p.A53T)) genes causing Parkinson's disease (PD) are common in Mediterranean populations. Variants in the Quinoid Dihydropteridine Reductase NM_000320 (QDPR c.68G > A (p.G23D)), Sepiapterin Reductase NM_003124 (SPR c.596-2A > G) and Methylenetetrahydrofolate Reductase NM_005957 (MTHFR c...
2016: BMC Medical Genetics
https://www.readbyqxmd.com/read/27610264/alpha-synuclein-in-parkinson-s-disease-from-pathogenetic-dysfunction-to-potential-clinical-application
#18
REVIEW
Lingjia Xu, Jiali Pu
Parkinson's disease is a neurodegenerative disease/synucleinopathy that develops slowly; however, there is no efficient method of early diagnosis, nor is there a cure. Progressive dopaminergic neuronal cell loss in the substantia nigra pars compacta and widespread aggregation of the α-synuclein protein (encoded by the SNCA gene) in the form of Lewy bodies and Lewy neurites are the neuropathological hallmarks of Parkinson's disease. The SNCA gene has undergone gene duplications, triplications, and point mutations...
2016: Parkinson's Disease
https://www.readbyqxmd.com/read/27581683/effects-of-alpha-synuclein-on-primary-spinal-cord-neurons-associated-with-apoptosis-and-cntf-expression
#19
Guo-Ying Feng, Jia Liu, You-Cui Wang, Zhen-Yu Wang, Yue Hu, Qing-Jie Xia, Yang Xu, Fei-Fei Shang, Mei-Rong Chen, Fang Wang, Xue Zhou, Ting-Hua Wang
Spinal cord injury (SCI) often causes neurological deficits with poor recovery; the treatment, however, is far from satisfaction, and the mechanisms remain unclear. Using immunohistochemistry and western blotting analysis, we found α-synuclein (SNCA) was significantly up-regulated in the spinal caudal segment of rats subjected to spinal cord transection at 3 days post-operation. Moreover, the role of SNCA on neuronal growth and apoptosis in vitro was determined by using overexpressing and interfering SNCA recombined plasmid vectors, and the underlying mechanism was detected by QRT-PCR and western blotting...
August 31, 2016: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/27567856/elevated-mrna-expression-and-low-methylation-of-snca-in-japanese-alzheimer-s-disease-subjects
#20
Yuta Yoshino, Takaaki Mori, Taku Yoshida, Kiyohiro Yamazaki, Yuki Ozaki, Tomoko Sao, Yu Funahashi, Jun-Ichi Iga, Shu-Ichi Ueno
Despite the continuing debate about the amyloid hypothesis in Alzheimer's disease (AD), the precise pathogenesis is still unclear. Mixed pathology is common and multiple different protein aggregates are seen in human postmortem brains. Aggregates consisting of the alpha-synuclein protein encoded by the Synuclein Alpha gene (SCNA) are common in both dementia with Lewy bodies and AD. We examined SNCA mRNA expression and methylation rates of the CpG island at intron 1 of SNCA in peripheral leukocytes in 50 AD and age- and sex-matched control subjects to verify whether alpha-synuclein pathology affects the AD pathogenesis...
October 18, 2016: Journal of Alzheimer's Disease: JAD
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