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https://www.readbyqxmd.com/read/28812939/removing-dysfunctional-mitochondria-from-axons-independent-of-mitophagy-under-pathophysiological-conditions
#1
Mei-Yao Lin, Xiu-Tang Cheng, Yuxiang Xie, Qian Cai, Zu-Hang Sheng
Chronic mitochondrial dysfunction has been implicated in major neurodegenerative diseases. Long-term cumulative pathological stress leads to axonal accumulation of damaged mitochondria. Therefore, the early removal of defective mitochondria from axons constitutes a critical step of mitochondrial quality control. We recently investigated the axonal mitochondrial response to mild stress in wild-type neurons and chronic mitochondrial defects in amyotrophic lateral sclerosis (ALS)- and Alzheimer disease (AD)-linked neurons...
August 16, 2017: Autophagy
https://www.readbyqxmd.com/read/28804798/probing-biological-redox-chemistry-with-large-amplitude-fourier-transformed-ac-voltammetry
#2
Hope Adamson, Alan M Bond, Alison Parkin
Biological electron-exchange reactions are fundamental to life on earth. Redox reactions underpin respiration, photosynthesis, molecular biosynthesis, cell signalling and protein folding. Chemical, biomedical and future energy technology developments are also inspired by these natural electron transfer processes. Further developments in techniques and data analysis are required to gain a deeper understanding of the redox biochemistry processes that power Nature. This review outlines the new insights gained from developing Fourier transformed ac voltammetry as a tool for protein film electrochemistry...
August 14, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28803490/parkin-pink1-and-dj1-as-possible-modulators-of-mtor-pathway-in-ganglioglioma
#3
Katarzyna Drapalo, Jaroslaw Jozwiak
Ganglioglioma (GG) is a non-malignant tumor classified as G1 by the WHO. Although we currently know that the neoplasm may result from the hyperactivity of protein kinase B (PKB or Akt) or extracellular-regulated kinase (Erk), which upregulates mammalian target of rapamycin kinase (mTOR) and leads to translation of proteins responsible for cell cycle regulation, there are still many questions to be answered. In the current paper we try to analyze the link between GG formation and activity of three proteins known to play a role in neuroprotection...
August 14, 2017: International Journal of Neuroscience
https://www.readbyqxmd.com/read/28802919/nonmotor-signs-in-genetic-forms-of-parkinson-s-disease
#4
Meike Kasten, Connie Marras, Christine Klein
Although only a minority (i.e., ~5%) of Parkinson's disease (PD) cases is due to well-defined genetic causes, important clues about the common, "idiopathic" PD (iPD) can be garnered from monogenic model diseases. Nonmotor signs (NMS) are also present in monogenic PD and reviewed in this chapter for the confirmed PD genes SNCA, LRRK2, VPS35, Parkin, PINK1, DJ-1, and the risk factor gene GBA. Within the context of the MDSGene database (www.mdsgene.org), we performed a systematic literature search and extracted information on cognitive decline, depression, psychotic signs and symptoms, autonomic signs and symptoms, anxiety, sleep disorder, and olfactory impairment...
2017: International Review of Neurobiology
https://www.readbyqxmd.com/read/28801875/nanoparticles-in-explosives-detection-the-state-of-the-art-and-future-directions
#5
William J Peveler, Sultan Ben Jaber, Ivan P Parkin
No abstract text is available yet for this article.
August 12, 2017: Forensic Science, Medicine, and Pathology
https://www.readbyqxmd.com/read/28801211/parkin-clearance-of-dysfunctional-mitochondria-regulates-ros-levels-and-increases-survival-of-human-chondrocytes
#6
Mohammad Y Ansari, Nazir M Khan, Imran Ahmad, Tariq M Haqqi
OBJECTIVE: Mitochondrial dysfunction, oxidative stress and chondrocyte death are important contributors to the development and pathogenesis of osteoarthritis (OA). In this study, we determined the expression and role of Parkin in the clearance of damaged/dysfunctional mitochondria, regulation of ROS levels and chondrocyte survival under pathological conditions. METHODS: Human chondrocytes were from the unaffected area of knee OA cartilage (n=12) and were stimulated with IL-1β to mimic pathological conditions...
August 8, 2017: Osteoarthritis and Cartilage
https://www.readbyqxmd.com/read/28799556/anterior-approach-white-line-advancement-technique-and-long-term-outcomes-in-the-correction-of-blepharoptosis
#7
C B Schulz, R Nicholson, A Penwarden, B Parkin
PurposeAnterior approach white line advancement presents a novel surgical option for correction of blepharoptosis. The technique draws on several advantages of other approaches. The aim of this study was to present outcomes using this technique at a minimum follow-up of 18 months.Patients and methodsParticipants having undergone anterior approach white line advancement ptosis correction at a single institution were retrospectively recruited at a minimum of 18 months' follow-up. A total of 18 independent eyelid measurements were recorded at final review...
August 11, 2017: Eye
https://www.readbyqxmd.com/read/28799502/mitochondrial-dynamics-and-proteins-related-to-neurodegenerative-diseases
#8
Athanasios Alexiou, Bilal Nizami, Faez Iqbal Khan, Georgia Soursou, Charalampos Vairaktarakis, Stylianos Chatzichronis, Vasilis Tsiamis, Vasileios Manztavinos, Nagendra Sastry Yarla, Ghulam Md Ashraf
Disruptions in the regulation of mitochondrial dynamics and the occurrence of proteins misfolding lead to neuronal death, resulting in Age-related Dementia and Neurodegenerative diseases as well as Frailty. Functional, neurophysiologic and biochemical alterations within the mitochondrial populations can reveal deficits in brain energy metabolism resulting in Mild Cognitive Impairment, abnormal neural development, autonomic dysfunction and other mitochondrial disorders. Additionally, in cases of Alzheimer's disease or Parkinson's disease, a significant number of proteins seems to form unordered and problematic structures, leading through unknown mechanisms to pathological conditions...
August 10, 2017: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/28798814/editorial-childhood-cancer-in-sub-saharan-africa
#9
EDITORIAL
Donald Maxwell Parkin, Cristina Stefan
Measurement of incidence rates of childhood cancer in Africa is difficult. The study 'Cancer of Childhood in sub Saharan Africa' [Stefan C, Bray F, Ferlay J, Parkin DM and Liu B (2017) Cancer of Childhood in sub-Saharan Africaecancer11(755)] brings together results from 16 population-based registries which, as members of the African Cancer Registry Network (AFCRN), have been evaluated as achieving adequate coverage of their target population. The cancers are classified according to the third revision of the International Classification of Childhood Cancer (ICCC-3) and recorded rates in Africa are compared with those in childhood populations in the UK, France, and the USA...
2017: Ecancermedicalscience
https://www.readbyqxmd.com/read/28795497/catastrophic-haemorrhage-from-button-battery-ingestion-in-children-a%C3%A2-growing-problem
#10
EDITORIAL
Katie Wright, Kate Parkins, Haiko Jahn, Rachel Rowlands, Ffion Davies
No abstract text is available yet for this article.
September 2017: Acta Paediatrica
https://www.readbyqxmd.com/read/28789629/early-onset-parkinson-s-disease-in-a-family-of-moroccan-origin-caused-by-a-p-a217d-mutation-in-pink1-a-case-report
#11
Brendan P Norman, Steven J Lubbe, Manuela Tan, Naomi Warren, Huw R Morris
BACKGROUND: Bi-allelic mutations in the genes Parkin (PARK2), PINK1 (PARK6) and DJ-1 (PARK7) are established causes of autosomal recessive early-onset Parkinson's Disease (EOPD). PINK1 mutations are the second commonest cause of EOPD. Specific mutations may be relatively common in certain populations because of a founder effect. Homozygous p.A217D PINK1 mutations were previously shown to cause EOPD in a large Sudanese kindred. CASE PRESENTATION: Here we report the segregation of homozygous PINK1 p...
August 8, 2017: BMC Neurology
https://www.readbyqxmd.com/read/28789606/-pharming-out-support-a-promising-approach-to-integrating-clinical-pharmacists-into-established-primary-care-medical-home-practices
#12
Kimberly D Brunisholz, Jeff Olson, Jonathan W Anderson, Emily Hays, Peggy M Tilbury, Bradley Winter, Josh Rickard, Sharon Hamilton, Gregory Parkin
Objective Embedding clinical pharmacists into ambulatory care settings needs to be assessed in the context of established medical home models. Methods A retrospective, observational study examined the effectiveness of the Intermountain Healthcare Collaborative Pharmacist Support Services (CPSS) program from 2012-2015 among adult patients diagnosed with diabetes mellitus (DM) and/or high blood pressure (HBP). Patients who attended this program were considered the intervention (CPSS) cohort. These patients were matched using propensity scores with a reference group (no-CPSS cohort) to determine the effect of achieving disease management goals and time to achievement...
January 1, 2017: Journal of International Medical Research
https://www.readbyqxmd.com/read/28782874/in-vivo-imaging-reveals-mitophagy-independence-in-the-maintenance-of-axonal-mitochondria-during-normal-aging
#13
Xu Cao, Haiqiong Wang, Zhao Wang, Qingyao Wang, Shuang Zhang, Yuanping Deng, Yanshan Fang
Mitophagy is thought to be a critical mitochondrial quality control mechanism in neurons and has been extensively studied in neurological disorders such as Parkinson's disease. However, little is known about how mitochondria are maintained in the lengthy neuronal axons in the context of physiological aging. Here, we utilized the unique Drosophila wing nerve model and in vivo imaging to rigorously profile changes in axonal mitochondria during aging. We revealed that mitochondria became fragmented and accumulated in aged axons...
August 7, 2017: Aging Cell
https://www.readbyqxmd.com/read/28768533/progression-of-pathology-in-pink1-deficient-mouse-brain-from-splicing-via-ubiquitination-er-stress-and-mitophagy-changes-to-neuroinflammation
#14
Sylvia Torres-Odio, Jana Key, Hans-Hermann Hoepken, Júlia Canet-Pons, Lucie Valek, Bastian Roller, Michael Walter, Blas Morales-Gordo, David Meierhofer, Patrick N Harter, Michel Mittelbronn, Irmgard Tegeder, Suzana Gispert, Georg Auburger
BACKGROUND: PINK1 deficiency causes the autosomal recessive PARK6 variant of Parkinson's disease. PINK1 activates ubiquitin by phosphorylation and cooperates with the downstream ubiquitin ligase PARKIN, to exert quality control and control autophagic degradation of mitochondria and of misfolded proteins in all cell types. METHODS: Global transcriptome profiling of mouse brain and neuron cultures were assessed in protein-protein interaction diagrams and by pathway enrichment algorithms...
August 2, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28767702/astragaloside-iv-ameliorates-diabetic-nephropathy-by-modulating-the-mitochondrial-quality-control-network
#15
Xinhui Liu, Wenjing Wang, Gaofeng Song, Xian Wei, Youjia Zeng, Pengxun Han, Dongtao Wang, Mumin Shao, Juan Wu, Huili Sun, Guoliang Xiong, Shunmin Li
The aim of this study was to investigate the effect and possible mechanism of Astragaloside IV (AS-IV) on retarding the progression of diabetic nephropathy (DN) in a type 2 diabetic animal model, db/db mice. Eight-week-old male db/db diabetic mice and their nondiabetic littermate control db/m mice were used in the present study. AS-IV was administered to the db/db mice by adding it to standard feed at a dose of 1g/kg for 12 weeks. Renal injury was assessed by urinary albumin excretion (UAE) and Periodic acid-Schiff staining...
2017: PloS One
https://www.readbyqxmd.com/read/28767222/assessing-different-e3-ligases-for-small-molecule-induced-protein-ubiquitination-and-degradation
#16
Philipp Ottis, Momar Toure, Philipp M Cromm, Eunhwa Ko, Jeffrey L Gustafson, Craig M Crews
Proteolysis Targeting Chimera (PROTAC) technology, the recruitment of E3 ubiquitin ligases to induce the degradation of a protein target, is rapidly impacting chemical biology, as well as modern drug development. Here, we explore the breadth of this approach by evaluating different E3 ubiquitin ligases engineered in their substrate binding domains to accept a recruiting ligand. Five out of six E3 ligases were found to be amenable to recruitment for target degradation. Taking advantage of the tight spatio-temporal control of inducing ubiquitination on a pre-selected target in living cells, we focused on two of the engineered E3 ligases, βTRCP and parkin, to characterize their ability to induce ubiquitination in comparison with the PROTAC-recruited endogenous E3 ligases VHL and cereblon...
August 2, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28767217/synthesis-and-physical-properties-of-phase-engineered-transition-metal-dichalcogenide-monolayer-heterostructures
#17
Carl H Naylor, William M Parkin, Zhaoli Gao, Joel Berry, Songsong Zhou, Qicheng Zhang, John Brandon McClimon, Liang Z Tan, Christopher E Kehayias, Meng-Qiang Zhao, Ram S Gona, Robert W Carpick, Andrew M Rappe, David J Srolovitz, Marija Drndic, Alan T Charlie Johnson
Heterostructures of transition metal dichalcogenides (TMDs) offer the attractive prospect of combining distinct physical properties derived from different TMD structures. Here we report direct chemical vapor deposition of in-plane monolayer heterostructures based on 1H-MoS2 and 1T'-MoTe2. The large lattice mismatch between these materials led to intriguing phenomena at their interface. Atomic force microscopy indicated buckling in the 1H region. Tip-enhanced Raman spectroscopy showed mode structure consistent with Te substitution in the 1H region during 1T'-MoTe2 growth...
August 2, 2017: ACS Nano
https://www.readbyqxmd.com/read/28765939/molecular-dynamics-simulations-of-human-e3-ubiquitin-ligase-parkin
#18
Shi Qiu, Shun Zhu, Shan Xu, Yanyan Han, Wen Liu, Ji Zuo
Human E3 ubiquitin protein ligase parkin (Parkin) mediates mitophagy to maintain mitochondrial homeostasis. Parkin mutations are common genetic causes of early onset familial Parkinson's disease. The molecular mechanism of Parkin activation has been widely studied with emerging evidence suggesting an essential role of the phosphorylated (phospho)‑ubiquitin interaction. However, the underlying mecha-nism of the phospho‑ubiquitin interaction remains elusive. In the present study, replica exchange molecular dynamics simulations were performed to examine the conformational dynamics of Parkin in monomer and phospho‑ubiquitin‑bound states...
August 2, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28761318/parkin-overexpression-protects-retinal-ganglion-cells-against-glutamate-excitotoxicity
#19
Xinxin Hu, Yi Dai, Xinghuai Sun
PURPOSE: To investigate the role of parkin in regulating mitochondrial homeostasis of retinal ganglion cells (RGCs) under glutamate excitotoxicity. METHODS: Rat RGCs were purified from dissociated retinal tissue with a modified two-step panning protocol. Cultured RGCs were transfected with parkin using an adenovirus system. The distribution and morphology of mitochondria in the RGCs were assessed with MitoTracker. The expression and distribution of parkin and optineurin proteins were measured with western blot analysis and immunofluorescence...
2017: Molecular Vision
https://www.readbyqxmd.com/read/28760928/parkin-promotes-proteasomal-degradation-of-misregulated-bax
#20
Zeynep Cakir, Kathrin Funk, Joachim Lauterwasser, Franziska Todt, Ralf M Zerbes, Aline Oelgeklaus, Atsushi Tanaka, Martin van der Laan, Frank Edlich
The pro-apoptotic BCL-2 protein BAX commits human cells to apoptosis by permeabilizing the outer mitochondrial membrane. BAX activation has been suggested to require the separation of helix α5 from α6 and thus the 'latch' from the 'core' domain among other conformational changes. Here we show that conformational changes in this region impair BAX translocation to the mitochondria and retrotranslocation back into the cytosol and therefore BAX inhibition, but not activation. Redirecting misregulated BAX to the mitochondria revealed an alternative mechanism of BAX inhibition...
July 31, 2017: Journal of Cell Science
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