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https://www.readbyqxmd.com/read/29330923/mutant-parkin-induced-parkinsonism-from-an-electrical-point-of-view-abnormal-excitatory-response-to-dopamine-resolved-after-substitution
#1
Negar Sadat Ahmadi
No abstract text is available yet for this article.
January 2018: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/29330382/sesn2-facilitates-mitophagy-by-helping-parkin-translocation-through-ulk1-mediated-beclin1-phosphorylation
#2
Ashish Kumar, Chandrima Shaha
Mitophagy, the selective degradation of mitochondria by autophagy, is crucial for the maintenance of healthy mitochondrial pool in cells. The critical event in mitophagy is the translocation of cytosolic Parkin, a ubiquitin ligase, to the surface of defective mitochondria. This study elucidates a novel role of SESN2/Sestrin2, a stress inducible protein, in mitochondrial translocation of PARK2/Parkin during mitophagy. The data demonstrates that SESN2 downregulation inhibits BECN1/Beclin1 and Parkin interaction, thereby preventing optimum mitochondrial accumulation of Parkin...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29328405/liraglutide-repairs-the-infarcted-heart-the-role-of-the-sirt1-parkin-mitophagy-pathway
#3
Huiying Qiao, Haiyan Ren, He Du, Minfang Zhang, Xiaofang Xiong, Rong Lv
Liraglutide is glucagon‑like peptide‑1 receptor agonist used for treating patients with type 2 diabetes mellitus. The present study aimed to investigate the role and mechanism of liraglutide in repairing the infarcted heart following myocardial infarction. The results of the present study demonstrated that amplification of the dose of liraglutide for ~28 days was able to reduce cardiac fibrosis, inflammatory responses and myocardial death in the post‑infarcted heart. In vitro, liraglutide protected cardiomyocyte mitochondria against the chronic hypoxic damage, inhibiting the mitochondrial apoptosis pathways...
January 2, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29327808/the-rocky-road-to-personalized-medicine-in-acute-myeloid-leukaemia
#4
REVIEW
Bryan Brinda, Irum Khan, Brian Parkin, Heiko Konig
Acute myeloid leukaemia (AML) is a malignant disorder of the myeloid blood lineage characterized by impaired differentiation and increased proliferation of hematopoietic precursor cells. Recent technological advances have led to an improved understanding of AML biology but also uncovered the enormous cytogenetic and molecular heterogeneity of the disease. Despite this heterogeneity, AML is mostly managed by a 'one-size-fits-all' approach consisting of intensive, highly toxic induction and consolidation chemotherapy...
January 12, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29325612/genetics-of-parkinson-disease
#5
Aloysius Domingo, Christine Klein
An understanding of the genetic etiology of Parkinson disease (PD) has become imperative for the modern-day neurologist. Although genetic forms cause only a minority of PD, the disease mechanisms they elucidate advance the understanding of idiopathic cases. Moreover, recently identified susceptibility variants contribute to complex-etiology PD and broaden the contribution of genetics beyond familial and early-onset cases. Dominantly inherited monogenic forms mimic idiopathic PD and are caused by mutations or copy number variations of SNCA, LRRK2, and VPS35...
2018: Handbook of Clinical Neurology
https://www.readbyqxmd.com/read/29325568/pink1-import-regulation-a-fine-system-to-convey-mitochondrial-stress-to-the-cytosol
#6
REVIEW
Shiori Sekine, Richard J Youle
Insights from inherited forms of parkinsonism suggest that insufficient mitophagy may be one etiology of the disease. PINK1/Parkin-dependent mitophagy, which helps maintain a healthy mitochondrial network, is initiated by activation of the PINK1 kinase specifically on damaged mitochondria. Recent investigation of this process reveals that import of PINK1 into mitochondria is regulated and yields a stress-sensing mechanism. In this review, we focus on the mechanisms of mitochondrial stress-dependent PINK1 activation that is exerted by regulated import of PINK1 into different mitochondrial compartments and how this offers strategies to pharmacologically activate the PINK1/Parkin pathway...
January 10, 2018: BMC Biology
https://www.readbyqxmd.com/read/29322780/signal-and-noise-in-fet-nanopore-devices
#7
William M Parkin, Marija Drndic
The combination of a nanopore with a local field-effect transistor (FET-nanopore), like a nanoribbon, nanotube, or nanowire, in order to sense single molecules translocating through the pore is promising for DNA sequencing at megahertz bandwidths. Previously, it was experimentally determined that the detection mechanism was due to local potential fluctuations that arise when an analyte enters a nanopore and constricts ion flow through it, rather than the theoretically proposed mechanism of direct charge coupling between the DNA and nanowire...
January 11, 2018: ACS Sensors
https://www.readbyqxmd.com/read/29320548/primed-for-death-law-enforcement-citizen-homicides-social-media-and-retaliatory-violence
#8
Vladimir Bejan, Matthew Hickman, William S Parkin, Veronica F Pozo
We examine whether retaliatory violence exists between law enforcement and citizens while controlling for any social media contagion effect related to prior fatal encounters. Analyzed using a trivariate dynamic structural vector-autoregressive model, daily time-series data over a 21-month period captured the frequencies of police killed in the line of duty, police deadly use of force incidents, and social media coverage. The results support a significant retaliatory violence effect against minorities by police, yet there is no evidence of retaliatory violence against law enforcement officers by minorities...
2018: PloS One
https://www.readbyqxmd.com/read/29319091/a-superhydrophilic-cement-coated-mesh-an-acid-alkali-and-organic-reagent-free-material-for-oil-water-separation
#9
Jinlong Song, Shude Li, Changlin Zhao, Yao Lu, Danyang Zhao, Jing Sun, Tamal Roy, Claire J Carmalt, Xu Deng, Ivan P Parkin
Extreme wettability materials applied for oil/water separation have become a research focus in modern society, owing to the large amounts of oil-containing industrial wastewater emissions and the frequent occurrence of oil spills. However, most of the methods to fabricate the extreme wettability materials involve toxic chemical reagents, complex chemical reaction processes, and dangerous operation processes. A new acid, alkali, and organic reagent-free cement-coated mesh was presented for the sustained separation of oil and water from oil/water mixtures...
January 10, 2018: Nanoscale
https://www.readbyqxmd.com/read/29314851/organometallic-zirconium-compounds-in-an-oxygen-rich-coordination-environment-synthesis-and-structural-characterization-of-tris-oxoimidazolyl-hydroboratozirconium-compounds
#10
Ahmed Al-Harbi, Matthew J Hammond, Gerard Parkin
A series of tris(oxoimidazolyl)hydroborato ligands, which serve as L2X [O3] donors, have been employed to obtain organometallic zirconium compounds in an uncommon oxygen-rich coordination environment. For example, Cp[ToMeBenz]ZrCl2 has been synthesized via the reaction of [ToMeBenz]Na with CpZrCl3 and bears a structural resemblance to the bent metallocene dichloride derivative Cp2ZrCl2. In addition, the half-sandwich counterparts [ToMeBenz]ZrCl3 and [ToBut]ZrCl3 have been obtained by metathesis of ZrCl4 with [ToMeBenz]Na and [ToBut]Na, respectively...
January 9, 2018: Inorganic Chemistry
https://www.readbyqxmd.com/read/29311685/synaptotagmin-11-is-a-critical-mediator-of-parkin-linked-neurotoxicity-and-parkinson-s-disease-like-pathology
#11
Changhe Wang, Xinjiang Kang, Li Zhou, Zuying Chai, Qihui Wu, Rong Huang, Huadong Xu, Meiqin Hu, Xiaoxuan Sun, Suhua Sun, Jie Li, Ruiying Jiao, Panli Zuo, Lianghong Zheng, Zhenyu Yue, Zhuan Zhou
Loss-of-function mutations in Parkin are the most common causes of autosomal recessive Parkinson's disease (PD). Many putative substrates of parkin have been reported; their pathogenic roles, however, remain obscure due to poor characterization, particularly in vivo. Here, we show that synaptotagmin-11, encoded by a PD-risk gene SYT11, is a physiological substrate of parkin and plays critical roles in mediating parkin-linked neurotoxicity. Unilateral overexpression of full-length, but not C2B-truncated, synaptotagmin-11 in the substantia nigra pars compacta (SNpc) impairs ipsilateral striatal dopamine release, causes late-onset degeneration of dopaminergic neurons, and induces progressive contralateral motor abnormalities...
January 8, 2018: Nature Communications
https://www.readbyqxmd.com/read/29311479/transcriptome-analysis-reveals-that-midnolin-regulates-mrna-expression-levels-of-multiple-parkinson-s-disease-causative-genes
#12
Yutaro Obara, Kuniaki Ishii
We recently found that 10.5% of sporadic Parkinson's disease (PD) patients lacked one copy of the midnolin (MIDN) gene. In addition, gene knock-down/out of MIDN caused down-regulation of parkin E3 ubiquitin ligase, indicating MIDN to be a novel PD-risk factor or causative gene. In this study, we performed RNA-sequencing and transcriptome analysis of Midn wild-type and knockout cells. Midn positively or negatively regulated the expression of a wide variety of genes, including causative familial PD genes, such as α-synuclein, parkin, and EIF4G1...
2018: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/29311115/miro-proteins-coordinate-microtubule-and-actin-dependent-mitochondrial-transport-and-distribution
#13
Guillermo López-Doménech, Christian Covill-Cooke, Davor Ivankovic, Els F Halff, David F Sheehan, Rosalind Norkett, Nicol Birsa, Josef T Kittler
In the current model of mitochondrial trafficking, Miro1 and Miro2 Rho-GTPases regulate mitochondrial transport along microtubules by linking mitochondria to kinesin and dynein motors. By generating Miro1/2 double-knockout mouse embryos and single- and double-knockout embryonic fibroblasts, we demonstrate the essential and non-redundant roles of Miro proteins for embryonic development and subcellular mitochondrial distribution. Unexpectedly, the TRAK1 and TRAK2 motor protein adaptors can still localise to the outer mitochondrial membrane to drive anterograde mitochondrial motility in Miro1/2 double-knockout cells...
January 8, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29307080/inhibition-of-peroxynitrite-induced-mitophagy-activation-attenuates-cerebral-ischemia-reperfusion-injury
#14
Jinghan Feng, Xingmiao Chen, Binghe Guan, Caiming Li, Jinhua Qiu, Jiangang Shen
Activated autophagy/mitophagy has been intensively observed in ischemic brain, but its roles remain controversial. Peroxynitrite (ONOO-), as a representative of reactive nitrogen species, is considered as a critical neurotoxic factor in mediating cerebral ischemia-reperfusion (I/R) injury, but its roles in autophagy/mitophagy activation remain unclear. Herein, we hypothesized that ONOO- could induce PINK1/Parkin-mediated mitophagy activation via triggering dynamin-related protein 1 (Drp1) recruitment to damaged mitochondria, contributing to cerebral I/R injury...
January 6, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29290944/mitochondrial-targeted-hsp90-inhibitor-gamitrinib-tpp-g-tpp-induces-pink1-parkin-dependent-mitophagy
#15
Fabienne C Fiesel, Elle D James, Roman Hudec, Wolfdieter Springer
Loss-of-function mutations in PINK1 or PARKIN are associated with early-onset Parkinson's disease. Upon mitochondrial stress, PINK1 and Parkin together mediate a response that protects cells from the accumulation of harmful, damaged mitochondria. PINK1, the upstream kinase accumulates on the mitochondrial surface and recruits the E3 ubiquitin ligase Parkin on site to ubiquitylate substrate proteins. The joint activity of both to generate phosphorylated poly-ubiquitin chains on the mitochondrial surface induces the recruitment of autophagy receptors and eventually whole organelles are cleared by autophagy...
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29285276/pilot-study-molecular-risk-factors-for-diagnosing-sporadic-parkinson-s-disease-based-on-gene-expression-in-blood-in-mptp-induced-rhesus-monkeys
#16
Liangqin Shi, Chao Huang, Qihui Luo, Yu Xia, Heng Liu, Like Li, Wentao Liu, Wenjing Ma, Jing Fang, Li Tang, Wen Zeng, Zhengli Chen
Clinical diagnosis of Parkinson's disease (PD) is characterized by the classical features of tremor, bradykinesia and rigidity, which are present only when more than 70%-80% degeneration of dopaminergic (DA) neurons in the substantia nigra. The lack of means for early diagnosis of PD has elicited interest in searching for its risk factors, which, by now, are almost obtained at a single time point in PD process, and little developing risk factors, obtained from completely normal situation to the onset or even advanced stage of PD in individual person which could monitor the progress of PD, are present...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29284690/ampk%C3%AE-2-protects-against-the-development-of-heart-failure-by-enhancing-mitophagy-via-pink1-phosphorylation
#17
Bei Wang, Jiali Nie, Lujin Wu, Yangyang Hu, Zeng Wen, Lingli Dong, Ming-Hui Zou, Chen Chen, Dao Wen Wang
Rationale: Mitochondrial dysfunction plays an important role in heart failure (HF). However, the molecular mechanisms regulating mitochondrial functions via selective mitochondrial autophagy (mitophagy) are poorly understood. Objective: We sought to determine the role of AMP-activated protein kinase (AMPK) in selective mitophagy during HF. Methods and Results: An isoform shift from AMPKα2 to AMPKα1 was observed in failing-heart samples from HF patients and transverse aortic constriction (TAC)-induced mice, accompanied by decreased mitophagy and mitochondrial function...
December 28, 2017: Circulation Research
https://www.readbyqxmd.com/read/29284178/what-is-the-current-practice-of-therapists-in-the-measurement-of-somatosensation-in-children-with-cerebral-palsy-and-other-neurological-disorders
#18
Corrin Walmsley, Susan Taylor, Timothy Parkins, Leeanne Carey, Sonya Girdler, Catherine Elliott
BACKGROUND/AIM: Somatosensation is the ability to detect and recognise body sensations such as touch, vibration, pressure, pain, temperature and proprioception. Cerebral palsy is a neurological disorder that is often accompanied by impairments in somatosensation. Current somatosensory assessments have limited psychometrics established for use with these children. The aim of this study was to identify therapists' current practice and perspectives related to the assessment of somatosensation in children with neurological disorders...
December 28, 2017: Australian Occupational Therapy Journal
https://www.readbyqxmd.com/read/29260454/neuroprotective-effect-of-treadmill-exercise-possibly-via-regulation-of-lysosomal-degradation-molecules-in-mice-with-pharmacologically-induced-parkinson-s-disease
#19
Dong-Joo Hwang, Jung-Hoon Koo, Ki-Cheon Kwon, Dong-Hoon Choi, Sung-Deuk Shin, Jae-Hoon Jeong, Hyun-Seob Um, Joon-Yong Cho
Dysfunction of mitophagy, which is a selective degradation of defective mitochondria for quality control, is known to be implicated in the pathogenesis of Parkinson's disease (PD). However, how treadmill exercise (TE) regulates mitophagy-related molecules in PD remains to be elucidated. Therefore, we aimed to investigate how TE regulates α-synuclein (α-syn)-induced neurotoxicity and mitophagy-related molecules in the nigro-striatal region of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-mice. Our data showed that TE exhibited a significant restoration of tyrosine hydroxylase and motor coordination with suppression of α-syn expression, hallmarks of PD, possibly via up-regulation of lysosomal degradation molecules, LAMP-2 and cathepsin L, with down-regulation of p62, LC3-II/LC3-I ratio, PINK1 and parkin in the substantia nigra of MPTP mice...
December 19, 2017: Journal of Physiological Sciences: JPS
https://www.readbyqxmd.com/read/29258892/enhanced-repair-of-uv-induced-dna-damage-by-1-25-dihydroxyvitamin-d3-in-skin-is-linked-to-pathways-that-control-cellular-energy
#20
Mark Stephen Rybchyn, Warusavithana Gunawardena Manori De Silva, Vanessa Bernadette Sequeira, Bianca Yuko McCarthy, Anthony Vincent Dilley, Katie Marie Dixon, Gary Mark Halliday, Rebecca Sara Mason
Inadequately repaired post-UV DNA damage results in skin cancers. DNA repair requires energy but skin cells have limited capacity to produce energy after UV insult. We examined whether energy supply is important for DNA repair after UV exposure, in the presence of 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3), which reduces UV-induced DNA damage and photocarcinogenesis in a variety of models. After UV exposure of primary human keratinocytes, the addition of 1,25(OH)2D3 increased unscheduled DNA synthesis, a measure of DNA repair...
December 16, 2017: Journal of Investigative Dermatology
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