Read by QxMD icon Read


Kelly L Stauch, Lance M Villeneuve, Phillip R Purnell, Sanjit Pandey, Chittibabu Guda, Howard S Fox
This article reports changes in the striatal non-synaptic mitochondrial proteome of DJ-1, Parkin, and PINK1 knockout (KO) rats at 3 months of age. DJ-1, Parkin, and PINK1 mutations cause autosomal-recessive parkinsonism. It is thought that loss of function of these proteins contributes to the onset and pathogenesis of Parkinson׳s disease (PD). As DJ-1, Parkin, and PINK1 have functions in the regulation of mitochondria, the dataset generated here highlights protein expression changes, which can be helpful for understanding pathological mitochondrial alterations...
December 2016: Data in Brief
Rui Kang, Ling Zeng, Yangchun Xie, Zhengwen Yan, Borong Zhou, Lizhi Cao, Daniel J Klionsky, Kevin J Tracey, Jianhua Li, Haichao Wang, Timothy R Billiar, Jianxin Jiang, Daolin Tang
Although the PINK1-PARK2 pathway contributes to the pathogenesis of Parkinson disease, its roles in sepsis (a major challenge for critical care) were previously unknown. Here, we show that pink1(-/-) and park2(-/-) mice are more sensitive to polymicrobial sepsis-induced multiple organ failure and death. The decrease in the circulating level of the neurotransmitter dopamine in pink1(-/-) and park2(-/-) mice accelerates the release of a late sepsis mediator, HMGB1, via HIF1A-dependent anaerobic glycolysis and subsequent NLRP3-dependent inflammasome activation...
October 18, 2016: Autophagy
Jianghu Zhu, Yi Qu, Zhenlang Lin, Fengyan Zhao, Li Zhang, Yang Huang, Changan Jiang, Dezhi Mu
The incidence of preterm birth is rising worldwide. Among preterm infants, many face a lifetime of neurologic impairments. Recent studies have revealed that systemic inflammation can sensitize the immature brain to hypoxic-ischemic (HI) injury. Therefore, it is important to identify the mechanisms involved in inflammation-sensitized HI injury in immature brains. PTEN-induced putative kinase 1 (PINK1) is a regulatory protein that is highly expressed in the brain. We have previously found that PINK1 gene knockout can protect matured brains from HI injury in postnatal day 10 mice...
October 11, 2016: Brain Research
Timothy Wai, Shotaro Saita, Hendrik Nolte, Sebastian Müller, Tim König, Ricarda Richter-Dennerlein, Hans-Georg Sprenger, Joaquin Madrenas, Mareike Mühlmeister, Ulrich Brandt, Marcus Krüger, Thomas Langer
The SPFH (stomatin, prohibitin, flotillin, HflC/K) superfamily is composed of scaffold proteins that form ring-like structures and locally specify the protein-lipid composition in a variety of cellular membranes. Stomatin-like protein 2 (SLP2) is a member of this superfamily that localizes to the mitochondrial inner membrane (IM) where it acts as a membrane organizer. Here, we report that SLP2 anchors a large protease complex composed of the rhomboid protease PARL and the i-AAA protease YME1L, which we term the SPY complex (for SLP2-PARL-YME1L)...
October 13, 2016: EMBO Reports
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
Lianggong Ding, Ye Lei, Yanping Han, Yuhong Li, Xunming Ji, Lei Liu
As fundamental processes in mitochondrial dynamics, mitochondrial fusion, fission and transport are regulated by several core components, including Miro. As an atypical Rho-like small GTPase with high molecular mass, the exchange of GDP/GTP in Miro may require assistance from a guanine nucleotide exchange factor (GEF). However, the GEF for Miro has not been identified. While studying mitochondrial morphology in Drosophila, we incidentally observed that the loss of vimar, a gene encoding an atypical GEF, enhanced mitochondrial fission under normal physiological conditions...
October 2016: PLoS Genetics
Diana A Olszewska, Tim Lynch
No abstract text is available yet for this article.
October 6, 2016: Movement Disorders: Official Journal of the Movement Disorder Society
Giuseppe Arena, Enza Maria Valente
The gene PINK1 [phosphatase and tensin homolog (PTEN)-induced putative kinase 1] encodes a serine/threonine kinase which was initially linked to the pathogenesis of a familial form of Parkinson's disease. Research on PINK1 has recently unravelled that its multiple functions extend well beyond neuroprotection, implicating this eclectic protein in a growing number of human pathologies, including cancer, diabetes, cardiopulmonary dysfunctions and inflammation. Extensive studies have identified PINK1 as a crucial player in the mitochondrial quality control pathway, required to label damaged mitochondria and promote their elimination through an autophagic process (mitophagy)...
October 4, 2016: Journal of Pathology
Huimin Gao, Zhaoyu Chen, Yongmei Fu, Xiaoyan Yang, Ruihui Weng, Rui Wang, Jianjun Lu, Mengqiu Pan, Kunlin Jin, Chris McElroy, Beisha Tang, Ying Xia, Qing Wang
The nuclear orphan receptor, Nur77 plays important roles in neuroimflammation, apoptosis, and dopaminergic neurodegeneration. We conducted a further mechanistic investigation into the association of Nur77 with cell death. Cytosporone B (Csn-B), an agonist for Nur77, and Nur77 knockdown were adopted in the 6-hydroxydopamine (OHDA)-lesioned PC12 cells to investigate the mechanisms underlying Nur77-mediated injury. The 6-OHDA incubation caused Nur77 translocation from the nucleus to cytosol and Endoplasm reticulum (ER) and induced co-localization of Tom20/Nur77 and Protein Disulfide Isomerase (PDI)/Nur77...
September 29, 2016: Scientific Reports
Evgeny Shlevkov, Tal Kramer, Jason Schapansky, Matthew J LaVoie, Thomas L Schwarz
The PTEN-induced putative kinase 1 (PINK1)/Parkin pathway can tag damaged mitochondria and trigger their degradation by mitophagy. Before the onset of mitophagy, the pathway blocks mitochondrial motility by causing Miro degradation. PINK1 activates Parkin by phosphorylating both Parkin and ubiquitin. PINK1, however, has other mitochondrial substrates, including Miro (also called RhoT1 and -2), although the significance of those substrates is less clear. We show that mimicking PINK1 phosphorylation of Miro on S156 promoted the interaction of Parkin with Miro, stimulated Miro ubiquitination and degradation, recruited Parkin to the mitochondria, and via Parkin arrested axonal transport of mitochondria...
October 11, 2016: Proceedings of the National Academy of Sciences of the United States of America
William J Smiles, Evelyn B Parr, Vernon G Coffey, Orly Lacham-Kaplan, John A Hawley, Donny M Camera
Alcohol ingestion decreases post-exercise rates of muscle protein synthesis, but the mechanism(s) (e.g., increased protein breakdown) underlying this observation are unknown. Autophagy is an intracellular "recycling" system required for homeostatic substrate and organelle turnover; its dysregulation may provoke apoptosis and lead to muscle atrophy. We investigated the acute effects of alcohol ingestion on autophagic cell signaling responses to a bout of concurrent (combined resistance- and endurance-based) exercise...
September 27, 2016: American Journal of Physiology. Endocrinology and Metabolism
Thomas W Bastian, William C von Hohenberg, Daniel J Mickelson, Lorene M Lanier, Michael K Georgieff
Iron deficiency (ID), with and without anemia, affects an estimated 2 billion people worldwide. ID is particularly deleterious during early-life brain development, leading to long-term neurological impairments including deficits in hippocampus-mediated learning and memory. Neonatal rats with fetal/neonatal ID anemia (IDA) have shorter hippocampal CA1 apical dendrites with disorganized branching. ID-induced dendritic structural abnormalities persist into adulthood despite normalization of the iron status. However, the specific developmental effects of neuronal iron loss on hippocampal neuron dendrite growth and branching are unknown...
September 27, 2016: Developmental Neuroscience
Christopher M Rose, Marta Isasa, Alban Ordureau, Miguel A Prado, Sean A Beausoleil, Mark P Jedrychowski, Daniel J Finley, J Wade Harper, Steven P Gygi
System-wide quantitative analysis of ubiquitylomes has proven to be a valuable tool for elucidating targets and mechanisms of the ubiquitin-driven signaling systems, as well as gaining insights into neurodegenerative diseases and cancer. Current mass spectrometry methods for ubiquitylome detection require large amounts of starting material and rely on stochastic data collection to increase replicate analyses. We describe a method compatible with cell line and tissue samples for large-scale quantification of 5,000-9,000 ubiquitylation forms across ten samples simultaneously...
September 21, 2016: Cell Systems
Sun Young Chung, Sarah Kishinevsky, Joseph R Mazzulli, John Graziotto, Ana Mrejeru, Eugene V Mosharov, Lesly Puspita, Parvin Valiulahi, David Sulzer, Teresa A Milner, Tony Taldone, Dimitri Krainc, Lorenz Studer, Jae-Won Shim
Parkinson's disease (PD) is characterized by the selective loss of dopamine neurons in the substantia nigra; however, the mechanism of neurodegeneration in PD remains unclear. A subset of familial PD is linked to mutations in PARK2 and PINK1, which lead to dysfunctional mitochondria-related proteins Parkin and PINK1, suggesting that pathways implicated in these monogenic forms could play a more general role in PD. We demonstrate that the identification of disease-related phenotypes in PD-patient-specific induced pluripotent stem cell (iPSC)-derived midbrain dopamine (mDA) neurons depends on the type of differentiation protocol utilized...
October 11, 2016: Stem Cell Reports
Chi-Jing Choong, Hideki Mochizuki
Parkinson's disease (PD) presents a relative selective localization of pathology to substantia nigra and well-defined motor symptoms caused by dopaminergic degeneration that makes it an ideal target for gene therapy. Parallel progress in viral vector systems enables the delivery of therapeutic genes directly into brain with reasonable safety along with sustained transgene expression. To date, gene therapy for PD that has reached clinical trial evaluation is mainly based on symptomatic approach that involves enzyme replacement strategy and restorative approach that depends on the addition of neurotrophic factors...
September 16, 2016: Journal of Neural Transmission
Pascale Baden, Michela Deleidi
Mitochondrial antigens can be presented by MHC molecules and initiate adaptive immune responses but the mechanisms of mitochondrial antigen presentation (MitAP) have remained mostly unknown. A recent study proposes a new model whereby MitAP is mediated by a vesicle transport pathway that is suppressed by the Parkinson's disease (PD) associated proteins PTEN-induced putative kinase 1 (PINK1) and Parkin. This discovery brings a new perspective on the link between mitochondrial dysfunction and autoimmunity in PD...
September 13, 2016: Trends in Immunology
I M Aparicio, J Espino, I Bejarano, A Gallardo-Soler, M L Campo, G M Salido, J A Pariente, F J Peña, J A Tapia
Macroautophagy (hereafter autophagy) is an evolutionarily highly conserved cellular process that participates in the maintenance of intracellular homeostasis through the degradation of most long-lived proteins and entire organelles. Autophagy participates in some reproductive events; however, there are not reports regarding the role of autophagy in the regulation of sperm physiology. Hence, the aim of this study was to investigate whether autophagy-related proteins are present and functionally active in human spermatozoa...
2016: Scientific Reports
Ya-Ping Yan, Bo Zhang, Yan-Fang Mao, Zhang-Yu Guo, Jun Tian, Guo-Hua Zhao, Jia-Li Pu, Wei Luo, Zhi-Yuan Ouyang, Bao-Rong Zhang
Dopa-responsive dystonia (DRD) comprises a heterogeneous group of movement disorders. A limited number of studies of Chinese patients with DRD have been reported. In the present study, we investigated the clinical and genetic features of 12 Chinese DRD families. Point mutation analysis of the GTP-cyclohydrolase I (GCH1), tyrosine hydroxylase (TH) and sepiapterin reductase (SPR) genes was conducted by direct sequencing. In addition, multiplex ligation-dependent probe amplification targeting GCH1 and TH was performed in "mutation-free" patients...
October 5, 2016: International Journal of Neuroscience
Chung-Han Hsieh, Atossa Shaltouki, Ashley E Gonzalez, Alexandre Bettencourt da Cruz, Lena F Burbulla, Erica St Lawrence, Birgitt Schüle, Dimitri Krainc, Theo D Palmer, Xinnan Wang
Mitochondrial movements are tightly controlled to maintain energy homeostasis and prevent oxidative stress. Miro is an outer mitochondrial membrane protein that anchors mitochondria to microtubule motors and is removed to stop mitochondrial motility as an early step in the clearance of dysfunctional mitochondria. Here, using human induced pluripotent stem cell (iPSC)-derived neurons and other complementary models, we build on a previous connection of Parkinson's disease (PD)-linked PINK1 and Parkin to Miro by showing that a third PD-related protein, LRRK2, promotes Miro removal by forming a complex with Miro...
August 25, 2016: Cell Stem Cell
Julian L Klosowiak, Sungjin Park, Kyle P Smith, Michael E French, Pamela J Focia, Douglas M Freymann, Sarah E Rice
Hereditary Parkinson's disease is commonly caused by mutations in the protein kinase PINK1 or the E3 ubiquitin ligase Parkin, which function together to eliminate damaged mitochondria. PINK1 phosphorylates both Parkin and ubiquitin to stimulate ubiquitination of dozens of proteins on the surface of the outer mitochondrial membrane. However, the mechanisms by which Parkin recognizes specific proteins for modification remain largely unexplored. Here, we show that the C-terminal GTPase (cGTPase) of the Parkin primary substrate human Miro is necessary and sufficient for efficient ubiquitination...
2016: Scientific Reports
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"