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https://www.readbyqxmd.com/read/28817115/administration-of-follicle-stimulating-hormone-induces-autophagy-via-upregulation-of-hif-1%C3%AE-in-mouse-granulosa-cells
#1
Jilong Zhou, Wang Yao, Chengyu Li, Wangjun Wu, Qifa Li, Honglin Liu
Recent studies reported the important role of autophagy in follicular development. However, the underlying molecular mechanisms remain elusive. In this study, we investigated the effect of follicle-stimulating hormone (FSH) on mouse granulosa cells (MGCs). Results indicated that autophagy was induced by FSH, which is known to be the dominant hormone regulating follicular development and granulosa cell (GC) proliferation. The activation of mammalian target of rapamycin (mTOR), a master regulator of autophagy, was inhibited during the process of MGC autophagy...
August 17, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28806787/antagonism-of-proteasome-inhibitor-induced-heme-oxygenase-1-expression-by-pink1-mutation
#2
Xiang-Jun Sheng, Hunag-Ju Tu, Wei-Lin Chien, Kai-Hsiang Kang, Dai-Hua Lu, Horng-Huei Liou, Ming-Jen Lee, Wen-Mei Fu
PTEN-induced putative kinase 1 (PINK1) is an integral protein in the mitochondrial membrane and maintains mitochondrial fidelity. Pathogenic mutations in PINK1 have been identified as a cause of early-onset autosomal recessive familial Parkinson's disease (PD). The ubiquitin proteasome pathway is associated with neurodegenerative diseases. In this study, we investigated whether mutations of PINK1 affects the cellular stress response following proteasome inhibition. Administration of MG132, a peptide aldehyde proteasome inhibitor, significantly increased the expression of heme oxygenase-1 (HO-1) in rat dopaminergic neurons in the substantia nigra and in the SH-SY5Y neuronal cell line...
2017: PloS One
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/28799502/mitochondrial-dynamics-and-proteins-related-to-neurodegenerative-diseases
#5
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/28789629/early-onset-parkinson-s-disease-in-a-family-of-moroccan-origin-caused-by-a-p-a217d-mutation-in-pink1-a-case-report
#6
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/28782874/in-vivo-imaging-reveals-mitophagy-independence-in-the-maintenance-of-axonal-mitochondria-during-normal-aging
#7
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
#8
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
#9
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/28733540/am1241-alleviates-mptp-induced-parkinson-s-disease-and-promotes-the-regeneration-of-da-neurons-in-pd-mice
#10
Jun Shi, Qiong Cai, Jingxing Zhang, Xiaolie He, Yigang Liu, Rongrong Zhu, Lingjing Jin
The main pathological feature of Parkinson's disease (PD) is the loss of dopaminergic neurons in the substantia nigra. In this study, we investigated the role of cannabinoid receptor 2 (CB2R) agonist AM1241 on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in a mouse model of PD. Upon treatment with AM1241, the decreased CB2R level in the PD mouse brain was reversed and the behavior score markedly elevated, accompanied with a dose-dependent increase of dopamine and serotonin. In addition, western blot assay and immunostaining results suggested that AM1241 significantly activated PI3K/Akt/MEK phosphorylation and increased the expression of Parkin and PINK1, both in the substantia nigra and hippocampus...
June 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28716706/characterization-of-a-presymptomatic-stage-in-a-drosophila-parkinson-s-disease-model-unveiling-dopaminergic-compensatory-mechanisms
#11
Daniela Molina-Mateo, Nicolás Fuenzalida-Uribe, Sergio Hidalgo, Claudia Molina-Fernández, Jorge Abarca, Rafaella V Zárate, Marcela Escandón, Reinaldo Figueroa, María Florencia Tevy, Jorge M Campusano
Parkinson disease (PD) is a degenerative disorder characterized by several motor symptoms including shaking, rigidity, slow movement and difficult walking, which has been associated to the death of nigro-striatal dopaminergic neurons. >90% of PD patients also present olfactory dysfunction. Although the molecular mechanisms responsible for this disease are not clear, hereditary PD is linked to mutations in specific genes, including the PTEN-induced putative kinase 1 (PINK1). In this work we provide for the first time a thorough temporal description of the behavioral effects induced by a mutation in the PINK1 gene in adult Drosophila, a previously described animal model for PD...
July 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28716427/influence-of-l-dopa-on-subtle-motor-signs-in-heterozygous-parkin-and-pink1-mutation-carriers
#12
Anne Weissbach, Inke R König, Katja Hückelheim, Peter P Pramstaller, Elisa Werner, Norbert Brüggemann, Vera Tadic, Katja Lohmann, Tobias Bäumer, Alexander Münchau, Meike Kasten, Christine Klein
INTRODUCTION: A latent nigrostriatal deficit and its possible clinical consequences in asymptomatic heterozygous Parkin and PINK1 mutation carriers (AMC) have been a matter of investigation in recent years. Notably, mild Parkinsonian signs in heterozygous mutation carriers can be so subtle that they may be missed if not specifically investigated. METHODS: We studied 15 heterozygous Parkin and PINK1 AMC and 18 age- and sex-matched mutation-negative controls using a standardized video, instructing the probands to perform relevant parts of the UPDRS III to investigate fine motor movements at baseline and after first-time L-Dopa administration...
July 8, 2017: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/28716221/parkin-mutation-may-be-associated-with-serious-akinesia-in-a-patient-with-parkinson-s-disease
#13
Yuto Uchihara, Hiroshi Kataoka, Hiroyo Yoshino, Ryogo Syobatake, Nobutaka Hattori, Satoshi Ueno
Acute akinesia (AA) is an unusual motor complication in Parkinson's disease (PD). Reported risk factors for AA include infection, trauma, surgical intervention, and the withdrawal of antiparkinsonian medication. Recently, patients with genetic PD were reported to have a three-fold risk of AA than patients with non-genetic PD. We describe a patient with PD associated with a Parkin mutation in whom serious akinesia developed. A 42-year-old man with exon 2 heterozygous deletion and exon 4 heterozygous deletion in the PARK2 gene showed five unexpected AA for several 12h...
August 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28698153/curcumin-prevents-cisplatin-induced-renal-alterations-in-mitochondrial-bioenergetics-and-dynamic
#14
Bibiana Ortega-Domínguez, Omar Emiliano Aparicio-Trejo, Fernando E García-Arroyo, Juan Carlos León-Contreras, Edilia Tapia, Eduardo Molina-Jijón, Rogelio Hernández-Pando, Laura Gabriela Sánchez-Lozada, Diana Barrera-Oviedo, José Pedraza-Chaverri
Cisplatin is widely used as chemotherapeutic agent for treatment of diverse types of cancer, however, acute kidney injury (AKI) is an important side effect of this treatment. Diverse mechanisms have been involved in cisplatin-induced AKI, such as oxidative stress, apoptosis and mitochondrial damage. On the other hand, curcumin is a polyphenol extracted from the rhizome of Curcuma longa L. Previous studies have shown that curcumin protects against the cisplatin-induced AKI; however, it is unknown whether curcumin can reduce alterations in mitochondrial bioenergetics and dynamic in this model...
September 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28689991/ubiquitin-phosphorylated-at-ser57-hyper-activates-parkin
#15
Susanna George, Sabrina M Wang, Yumin Bi, Margot Treidlinger, Kathryn R Barber, Gary S Shaw, Patrick O'Donoghue
Malfunction of the ubiquitin (Ub) E3 ligase, parkin, leads to defects in mitophagy and protein quality control linked to Parkinson's disease. Parkin activity is stimulated by phosphorylation of Ub at Ser65 (pUb(S65)). Since the upstream kinase is only known for Ser65 (PINK1), the biochemical function of other phosphorylation sites on Ub remain largely unknown. We used fluorescently labelled and site-specifically phosphorylated Ub substrates to quantitatively relate the position and stoichiometry of Ub phosphorylation to parkin activation...
July 6, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28685977/the-post-therapeutic-effect-of-rapamycin-in-mild-traumatic-brain-injured-rats-ensuing-in-the-upregulation-of-autophagy-and-mitophagy
#16
Changxing Wang, Zhiying Hu, Yang Zou, Mingjun Xiang, Yuting Jiang, Benson O A Botchway, Xue Huo, Xiaoxue Du, Marong Fang
Mild traumatic brain injury (mTBI), common in juveniles, has been reported to be caused by sports-related concussion. Many young children may suffer from post-concussion syndrome. mTBI, in early stages of life, could play a part in neuron apoptosis and degeneration, cognitive and motor coordination impairment, as well as dementia. Our study was aimed at further investigating the post-therapeutic efficacy of rapamycin in the recuperation of mTBI while at the same time investigating the metamorphosis in both autophagy and mitophagy in mTBI...
September 2017: Cell Biology International
https://www.readbyqxmd.com/read/28684172/efficient-prevention-of-neurodegenerative-diseases-by-depletion-of-starvation-response-factor-ataxin-2
#17
REVIEW
Georg Auburger, Nesli-Ece Sen, David Meierhofer, Ayşe-Nazlı Başak, Aaron D Gitler
Ataxin-2 (ATXN2) homologs exist in all eukaryotic organisms and may have contributed to their origin. Apart from a role in endocytosis, they are known for global effects on mRNA repair and ribosomal translation. Cell size, protein synthesis, and fat and glycogen storage are repressed by ATXN2 via mTORC1 signaling. However, specific liver mitochondrial matrix enzymes and the mitochondrial repair factor PINK1 require ATXN2 abundance. During periods of starvation, ATXN2 is transcriptionally induced and localized to cytosolic stress granules, where nuclear factors dock to compensate RNA pathology...
July 3, 2017: Trends in Neurosciences
https://www.readbyqxmd.com/read/28683321/the-ubiquitination-of-pink1-is-restricted-to-its-mature-52-kda-form
#18
Yuhui Liu, Cristina Guardia-Laguarta, Jiang Yin, Hediye Erdjument-Bromage, Brittany Martin, Michael James, Xuejun Jiang, Serge Przedborski
Along with Parkin, PINK1 plays a critical role in maintaining mitochondrial quality control. Although PINK1 is expressed constitutively, its level is kept low in healthy mitochondria by polyubiquitination and ensuing proteasomal degradation of its mature, 52 kDa, form. We show here that the target of PINK1 polyubiquitination is the mature form and is mediated by ubiquitination of a conserved lysine at position 137. Notably, the full-length protein also contains Lys-137 but is not ubiquitinated. On the basis of our data, we propose that cleavage of full-length PINK1 at Phe-104 disrupts the major hydrophobic membrane-spanning domain in the protein, inducing a conformation change in the resultant mature form that exposes Lys-137 to the cytosol for subsequent modification by the ubiquitination machinery...
July 5, 2017: Cell Reports
https://www.readbyqxmd.com/read/28681509/akt2-ablation-prolongs-life-span-and-improves-myocardial-contractile-function-with-adaptive-cardiac-remodeling-role-of-sirt1-mediated-autophagy-regulation
#19
Jun Ren, Lifang Yang, Li Zhu, Xihui Xu, Asli F Ceylan, Wei Guo, Jian Yang, Yingmei Zhang
Aging is accompanied with unfavorable geometric and functional changes in the heart involving dysregulation of Akt and autophagy. This study examined the impact of Akt2 ablation on life span and cardiac aging as well as the mechanisms involved with a focus on autophagy and mitochondrial integrity. Cardiac geometry, contractile, and intracellular Ca(2+) properties were evaluated using echocardiography, IonOptix(®) edge-detection and fura-2 techniques. Levels of Sirt1, mitochondrial integrity, autophagy, and mitophagy markers were evaluated using Western blot...
July 5, 2017: Aging Cell
https://www.readbyqxmd.com/read/28673964/sorafenib-targets-the-mitochondrial-electron-transport-chain-complexes-and-atp-synthase-to-activate-the-pink1-parkin-pathway-and-modulate-cellular-drug-response
#20
Conggang Zhang, Zeyu Liu, Eric Bunker, Adrian Ramirez, Schuyler Lee, Yinghua Peng, Aik Choon Tan, S Gail Eckhardt, Douglas A Chapnick, Xuedong Liu
Sorafenib (Nexavar) is a broad-spectrum multi-kinase inhibitor that proves effective in treating advanced renal-cell carcinoma and liver cancer. Despite its well-characterized mechanism of action on several established cancer-related protein kinases, sorafenib causes variable responses among human tumors, although the cause for this variation is unknown. In an unbiased screening of an oncology drug library, we found that sorafenib activates recruitment of the ubiquitin E3 ligase Parkin to damaged mitochondria...
July 3, 2017: Journal of Biological Chemistry
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