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parkinson's disease and autophagy

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https://www.readbyqxmd.com/read/28821398/urate-promotes-snca-%C3%AE-synuclein-clearance-via-regulating-mtor-dependent-macroautophagy
#1
Yu-Lan Sheng, Xing Chen, Xiao-Ou Hou, Xin-Yuan, Bao-Shi Yuan, Yu-Qing Yuan, Qi-Lin Zhang, Xian Cao, Chun-Feng Liu, Wei-Feng Luo, Li-Fang Hu
Serum urate levels are reported to be significantly lowered in patients with Parkinson's disease (PD) and inversely correlated to the risk and progression of PD. However, the mechanism by which urate affects PD is poorly understood. Here we showed that treatment with uric acid (UA) resulted in an autophagy activity enhancement in PC12 cells in dose- and time-dependent manners, as indicated by LC3-II increase and P62 decrease. Moreover, UA was still able to increase the LC3-II level and the number of LC3 puncta in the presence of Bafilomycin A1, a lysosomal inhibitor...
August 15, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28803490/parkin-pink1-and-dj1-as-possible-modulators-of-mtor-pathway-in-ganglioglioma
#2
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/28802652/an-autophagic-mechanism-is-involved-in-the-6-hydroxydopamine-induced-neurotoxicity-in-vivo
#3
Xin He, Wei Yuan, Zijian Li, Juan Feng
6-hydroxydopamine (6-OHDA) is one of the most common agents for modeling dopaminergic neuron degeneration in Parkinson's disease (PD). So far, the role of autophagy in 6-OHDA-induced neurotoxicity remains controversial and most evidence is collected from in vitro studies. In this study, we determined the role of autophagy activation in 6-OHDA-induced neurotoxicity in a rat model of PD. Following 6-OHDA treatment, we observed a concomitant activation of autophagy and apoptosis. To further explore the interaction between autophagy and apoptosis induced by 6-OHDA, autophagy inhibitor 3-methylademine (3-MA) or cysteine protease inhibitor Z-FA-fmk was applied...
August 9, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28797885/mitophagy-in-neurodegenerative-diseases
#4
REVIEW
Carlo Rodolfo, Silvia Campello, Francesco Cecconi
Neurodegenerative diseases, such as Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's disease (HD), and Amyotrophic Lateral Sclerosis (ALS), are a complex "family" of pathologies, characterised by the progressive loss of neurons and/or neuronal functions, leading to severe physical and cognitive inabilities in affected patients. These syndromes, despite differences in the causative events, the onset, and the progression of the disease, share as common features the presence of aggregate-prone neuro-toxic proteins, in the form of aggresomes and/or inclusion bodies, perturbing cellular homeostasis and neuronal function (Popovic et al...
August 8, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28796567/receptors-make-the-pathway-choice-for-protein-degradation
#5
Yuchen Feng, Daniel J Klionsky
Damaged or aggregated proteins and organelles accumulate with age and contribute to various age-related pathologies including Alzheimer, Parkinson or Huntington diseases. In eukaryotic cells, there are two major pathways for degradation of the cytoplasm: The ubiquitin-proteasome system (UPS) and macroautophagy/autophagy. Both pathways can share the characteristic of initiating the process by ubiquitination of the substrate, but they utilize different ubiquitin receptors. In a paper described in a punctum in this issue, Lu et al...
August 10, 2017: Autophagy
https://www.readbyqxmd.com/read/28790319/novel-animal-model-defines-genetic-contributions-for-neuron-to-neuron-transfer-of-%C3%AE-synuclein
#6
Trevor Tyson, Megan Senchuk, Jason F Cooper, Sonia George, Jeremy M Van Raamsdonk, Patrik Brundin
Cell-to-cell spreading of misfolded α-synuclein (α-syn) is suggested to contribute to the progression of neuropathology in Parkinson's disease (PD). Compelling evidence supports the hypothesis that misfolded α-syn transmits from neuron-to-neuron and seeds aggregation of the protein in the recipient cells. Furthermore, α-syn frequently appears to propagate in the brains of PD patients following a stereotypic pattern consistent with progressive spreading along anatomical pathways. We have generated a C. elegans model that mirrors this progression and allows us to monitor α-syn neuron-to-neuron transmission in a live animal over its lifespan...
August 8, 2017: Scientific Reports
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/28766175/backbone-and-side-chain-resonance-assignments-for-a-structured-domain-within-atg32
#8
Xue Xia, Maria Pellegrini, Michael J Ragusa
Autophagy is a catabolic cellular process that targets cytosolic material, including mitochondria, to the vacuole or lysosomes for degradation. The selective degradation of mitochondria by autophagy is termed mitophagy. Dysfunctional mitophagy, which leads to the accumulation of damaged mitochondria, has been implicated in Parkinson's disease, cancer, cardiac disease and metabolic disease. In Saccharomyces cerevisiae, mitophagy is initiated by the autophagy receptor Atg32, an outer mitochondrial membrane protein...
August 1, 2017: Biomolecular NMR Assignments
https://www.readbyqxmd.com/read/28764914/breaking-down-autophagy-and-the-ubiquitin-proteasome-system
#9
Shinae Jung, Yuhyun Chung, Young J Oh
Autophagy is an evolutionarily conserved catabolic process that is involved in cellular homeostasis and stress responses. Although basal levels of autophagy are essential for cellular homeostasis, dysregulated autophagy is linked to neurodegeneration. Recent studies using genetic or neurotoxin-based models of Parkinson's disease (PD) detect autophagy. We demonstrate that neurotoxins induce autophagy in dopaminergic neuronal cell line and primary cultured neurons. Based on previous reports, including ones from our laboratory, which show that elevated reactive oxygen species (ROS) and cytosolic calcium are implicated in dopaminergic neurodegeneration, we reasoned that these triggers may play critical roles in determining dysregulated autophagy...
July 26, 2017: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/28760440/the-effect-of-electroacupuncture-on-proteomic-changes-in-the-motor-cortex-of-6-ohda-parkinsonian-rats
#10
Min Li, Lijuan Li, Ke Wang, Wenting Su, Jun Jia, Xiaomin Wang
Electroacupuncture (EA) has been reported to alleviate motor deficits in Parkinson's disease (PD) patients, and PD animal models. However, the mechanisms by which EA improves motor function have not been investigated. We have employed a 6-hydroxydopamine (6-OHDA) unilateral injection induced PD model to investigate whether EA alters protein expression in the motor cortex. We found that 4 weeks of EA treatment significantly improved spontaneous floor plane locomotion and rotarod performance. High-throughput proteomic analysis in the motor cortex was employed...
July 28, 2017: Brain Research
https://www.readbyqxmd.com/read/28755477/thioredoxin-interacting-protein-induced-%C3%AE-synuclein-accumulation-via-inhibition-of-autophagic-flux-implications-for-parkinson-s-disease
#11
Cun-Jin Su, Yu Feng, Teng-Teng Liu, Xu Liu, Jun-Jie Bao, Ai-Ming Shi, Duan-Min Hu, Tong Liu, Yun-Li Yu
AIMS: Thioredoxin-interacting protein (TXNIP) is associated with activation of oxidative stress through inhibition of thioredoxin (Trx). However, some evidences point out that TXNIP acts as a scaffolding protein in signaling complex independent of cellular redox regulation. The autophagy-lysosomal pathway plays important roles in the clearance of misfolded proteins and dysfunctional organelles. Lysosomal dysfunction has been involved in several neurodegenerative disorders including Parkinson's disease (PD)...
July 29, 2017: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/28741160/erratum-to-treadmill-exercise-attenuates-%C3%AE-synuclein-levels-by-promoting-mitochondrial-function-and-autophagy-possibly-via-sirt1-in-the-chronic-mptp-p-induced-mouse-model-of-parkinson-s-disease
#12
https://www.readbyqxmd.com/read/28738770/effects-of-resveratrol-and-other-polyphenols-on-the-most-common-brain-age-related-diseases
#13
Fiorella Sarubbo, David Moranta, Victor Jose Asensio, Antonio Miralles, Susana Esteban
With the global increase in the elderly population, modern societies must meet the challenge to find strategies to reduce the consequences of aging process; thereby decreasing the incidence of age-related neurodegenerative diseases. Over the last two decades, oxidative stress and recently inflammation, have been pointed out as the leading causes of brain aging. As a suggested treatment, the consumption or administration of antioxidant and anti-inflammatory molecules, such as polyphenols, present in food, is recommended as a beneficial strategy for preventing brain aging and several brain age-related diseases...
July 24, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28734275/low-level-of-autophagy-related-gene-10-atg10-expression-in-the-6-hydroxydopamine-rat-model-of-parkinson-s-disease
#14
Marzieh Shams Nooraei, Ali Noori-Zadeh, Shahram Darabi, Farzad Rajaei, Zohreh Golmohammadi, Hojjat Allah Abbaszadeh
Background: Autophagy is a mechanism disassembling the damaged organelles from the cell. This study attempted to examine the expression of several autophagy-related genes in Parkinson’s disease (PD) rat model. Methods: The male Wistar rats were divided into three groups as control, sham, and lesion. In the latter group, the PD rat model was induced by the injection of 6-hydroxydopamine in the striatum.The behavioral test was conducted one (baseline) and four weeks after the surgery through apomorphine hydrochloride...
July 23, 2017: Iranian Biomedical Journal
https://www.readbyqxmd.com/read/28733899/6-ohda-induces-oxidation-of-f-box-protein-fbw7%C3%AE-by-chaperone-mediated-autophagy-in-parkinson-s-model
#15
Xiufeng Wang, Heng Zhai, Fang Wang
Parkinson's disease (PD) is the most common movement disorder disease, and its pathological feature is the degenerative loss of dopaminergic neurons in the substantia nigra compacta (SNc). In this study, we investigated whether distinct stress conditions target F-box protein Fbw7β via converging mechanisms. Our results showed that the 6-hyroxydopamine (6-OHDA), which causes PD in animals' models, led to decreased stability of Fbw7β in DA neuronal SN4741 cells. Further experiments suggested that oxidized Fbw7β bound to heat-shock cognate protein 70 kDa, the key regulator for chaperone-mediated autophagy (CMA), at a higher affinity...
July 22, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28724388/o-glcnac-regulation-of-autophagy-and-%C3%AE-synuclein-homeostasis-implications-for-parkinson-s-disease
#16
Willayat Y Wani, Xiaosen Ouyang, Gloria A Benavides, Matthew Redmann, Stacey S Cofield, John J Shacka, John C Chatham, Victor Darley-Usmar, Jianhua Zhang
Post-translational modification on protein Ser/Thr residues by O-linked attachment of ß-N-acetyl-glucosamine (O-GlcNAcylation) is a key mechanism integrating redox signaling, metabolism and stress responses. One of the most common neurodegenerative diseases that exhibit aberrant redox signaling, metabolism and stress response is Parkinson's disease, suggesting a potential role for O-GlcNAcylation in its pathology. To determine whether abnormal O-GlcNAcylation occurs in Parkinson's disease, we analyzed lysates from the postmortem temporal cortex of Parkinson's disease patients and compared them to age matched controls and found increased protein O-GlcNAcylation levels...
July 19, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28721811/moving-to-the-rhythm-with-clock-circadian-genes-autophagy-mtor-and-sirt1-in-degenerative-disease-and-cancer
#17
Kenneth Maiese
BACKGROUND: The mammalian circadian clock and its associated clock genes are increasingly be recognized as critical components for a number of physiological and disease processes that extend beyond hormone release, thermal regulation, and sleep-wake cycles. New evidence suggests that clinical behavior disruptions that involve prolonged shift work and even space travel may negatively impact circadian rhythm and lead to multi-system disease. METHODS: In light of the significant role circadian rhythm can hold over the body's normal physiology as well as disease processes, we examined and discussed the impact circadian rhythm and clock genes hold over lifespan, neurodegenerative disorders, and tumorigenesis...
July 17, 2017: Current Neurovascular Research
https://www.readbyqxmd.com/read/28721631/1-trichloromethyl-1-2-3-4-tetrahydro-beta-carboline-taclo-alters-cell-cycle-progression-in-human-neuroblastoma-cell-lines
#18
Rakesh Kumar Sharma, Eduardo Candelario-Jalil, Doris Feineis, Gerhard Bringmann, Bernd L Fiebich, Ravi Shankar Akundi
1-Trichloromethyl-1,2,3,4-tetrahydro-β-carboline, abbreviated as TaClo, is an endogenous neurotoxin capable of formation in the brain through the condensation of neuronal tryptamine with ingested exogenous toxins such as trichloroethylene or chloral hydrate. Due to its structural resemblance to 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP), and similar ability to inhibit mitochondrial complex I, TaClo has been implicated in the etiology of Parkinson's disease. Previous studies have shown the cytotoxicity of TaClo in various cell culture models...
July 18, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28713240/the-coordinated-action-of-calcineurin-and-cathepsin-d-protects-against-%C3%AE-synuclein-toxicity
#19
Andreas Aufschnaiter, Lukas Habernig, Verena Kohler, Jutta Diessl, Didac Carmona-Gutierrez, Tobias Eisenberg, Walter Keller, Sabrina Büttner
The degeneration of dopaminergic neurons during Parkinson's disease (PD) is intimately linked to malfunction of α-synuclein (αSyn), the main component of the proteinaceous intracellular inclusions characteristic for this pathology. The cytotoxicity of αSyn has been attributed to disturbances in several biological processes conserved from yeast to humans, including Ca(2+) homeostasis, general lysosomal function and autophagy. However, the precise sequence of events that eventually results in cell death remains unclear...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28710704/systemic-analysis-of-mirnas-in-pd-stress-condition-mir-5701-modulates-mitochondrial-lysosomal-cross-talk-to-regulate-neuronal-death
#20
Paresh Prajapati, Lakshmi Sripada, Kritarth Singh, Milton Roy, Khyati Bhatelia, Pooja Dalwadi, Rajesh Singh
Parkinson's disease (PD) is complex neurological disorder and is prevalent in the elderly population. This is primarily due to loss of dopaminergic neurons in the substantia nigra pars compacta (SNc) region of the brain. The modulators of the selective loss of dopaminergic neurons in PD are still not well understood. The small non-coding RNAs specifically miRNAs fine-tune the protein levels by post-transcriptional gene regulation. The role of miRNAs in PD pathogenesis is still not well characterized. In the current study, we identified the miRNA expression pattern in 6-OHDA-induced PD stress condition in SH-SY5Y, dopaminergic neuronal cell line...
July 14, 2017: Molecular Neurobiology
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