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parkinson's disease and autophagy

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https://www.readbyqxmd.com/read/27913668/cellular-functions-of-lrrk2-implicate-vesicular-trafficking-pathways-in-parkinson-s-disease
#1
REVIEW
Mark R Cookson
Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene, associated with Parkinson's disease, have been shown to affect intracellular trafficking pathways in a variety of cells and organisms. An emerging theme is that LRRK2 can bind to multiple membranous structures in cells, and several recent studies have suggested that the Rab family of small GTPases might be important in controlling the recruitment of LRRK2 to specific cellular compartments. Once localized to membranes, LRRK2 then influences downstream events, evidenced by changes in the autophagy-lysosome pathway...
December 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27908782/adaptive-responses-of-neuronal-mitochondria-to-bioenergetic-challenges-roles-in-neuroplasticity-and-disease-resistance
#2
REVIEW
Sophia M Raefsky, Mark P Mattson
An important concept in neurobiology is "neurons that fire together, wire together" which means that the formation and maintenance of synapses is promoted by activation of those synapses. Very similar to the effects of the stress of exercise on muscle cells, emerging findings suggest that neurons respond to activity by activating signaling pathways (e.g., Ca(2+), CREB, PGC-1α, NF-κB) that stimulate mitochondrial biogenesis and cellular stress resistance. These pathways are also activated by aerobic exercise and food deprivation, two bioenergetic challenges of fundamental importance in the evolution of the brains of all mammals, including humans...
November 29, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27890431/neuroprotective-mechanisms-of-plant-extracts-against-mptp-induced-neurotoxicity-future-applications-in-parkinson-s-disease
#3
REVIEW
Abdelrahman Ibrahim Abushouk, Ahmed Negida, Hussien Ahmed, Mohamed M Abdel-Daim
Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease, affecting about seven to 10 million patients worldwide. The major pathological features of PD are loss of dopaminergic neurons in the nigrostriatal pathway and accumulation of alpha-synuclein molecules, forming Lewy bodies. Until now, there is no effective cure for PD, and investigators are searching for neuroprotective strategies to stop or slow the disease progression. The MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) induced neurotoxicity of the nigrostriatal pathway has been used to initiate PD in animal models...
November 24, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27889578/molecular-neurobiology-of-mtor
#4
REVIEW
Katarzyna Switon, Katarzyna Kotulska, Aleksandra Janusz-Kaminska, Justyna Zmorzynska, Jacek Jaworski
Mammalian/mechanistic target of rapamycin (mTOR) is a serine-threonine kinase that controls several important aspects of mammalian cell function. mTOR activity is modulated by various intra- and extracellular factors; in turn, mTOR changes rates of translation, transcription, protein degradation, cell signaling, metabolism, and cytoskeleton dynamics. mTOR has been repeatedly shown to participate in neuronal development and the proper functioning of mature neurons. Changes in mTOR activity are often observed in nervous system diseases, including genetic diseases (e...
November 23, 2016: Neuroscience
https://www.readbyqxmd.com/read/27888296/toll-like-receptor-2-is-increased-in-neurons-in-parkinson-s-disease-brain-and-may-contribute-to-alpha-synuclein-pathology
#5
Nicolas Dzamko, Amanda Gysbers, Gayathri Perera, Anita Bahar, Amrita Shankar, Jianqun Gao, YuHong Fu, Glenda M Halliday
Inflammation is likely a key contributor to the pathogenesis of Parkinson's disease (PD), a progressively debilitating neurodegenerative disease that is accompanied by a pathological accumulation of the α-synuclein protein in a staged manner through the brain. What leads to the accumulation of α-synuclein in PD and how this relates to inflammatory pathways, however, is not entirely clear. Toll-like receptor (TLR) signaling is a major pathway mediating inflammation and, in particular, TLR2 is increasingly being implicated in PD...
November 25, 2016: Acta Neuropathologica
https://www.readbyqxmd.com/read/27882077/potential-protective-effects-of-autophagy-activated-in-mpp-treated-astrocytes
#6
Cunzhou Shen, Wenbiao Xian, Hongyan Zhou, Ling Chen, Zhong Pei
Astrocytes, which have various important functions, have previously been associated with Parkinsons disease (PD), particularly in 1-methyl-4-phenylpyridinium (MPP+) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) models of PD. MPP+ is the toxic metabolite of MPTP and is generated by the enzymatic activity of monoamine oxidase B, which is predominantly located in astrocytes. MPP+ acts as a mitochondrial complex I inhibitor. Autophagy is an evolutionarily conserved self-digestion pathway in eukaryotic cells, which occurs in response to various types of stress, including starvation and oxidative stress...
November 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27857176/glycation-potentiates-neurodegeneration-in-models-of-huntington-s-disease
#7
Hugo Vicente Miranda, Marcos António Gomes, Joana Branco-Santos, Carlo Breda, Diana F Lázaro, Luísa Vaqueiro Lopes, Federico Herrera, Flaviano Giorgini, Tiago Fleming Outeiro
Protein glycation is an age-dependent posttranslational modification associated with several neurodegenerative disorders, including Alzheimer's and Parkinson's diseases. By modifying amino-groups, glycation interferes with folding of proteins, increasing their aggregation potential. Here, we studied the effect of pharmacological and genetic manipulation of glycation on huntingtin (HTT), the causative protein in Huntington's disease (HD). We observed that glycation increased the aggregation of mutant HTT exon 1 fragments associated with HD (HTT72Q and HTT103Q) in yeast and mammalian cell models...
November 18, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27852774/a-drosophila-model-of-neuronopathic-gaucher-disease-demonstrates-lysosomal-autophagic-defects-and-altered-mtor-signalling-and-is-functionally-rescued-by-rapamycin
#8
Kerri J Kinghorn, Sebastian Grönke, Jorge Iván Castillo-Quan, Nathaniel S Woodling, Li Li, Ernestas Sirka, Matthew Gegg, Kevin Mills, John Hardy, Ivana Bjedov, Linda Partridge
Glucocerebrosidase (GBA1) mutations are associated with Gaucher disease (GD), an autosomal recessive disorder caused by functional deficiency of glucocerebrosidase (GBA), a lysosomal enzyme that hydrolyzes glucosylceramide to ceramide and glucose. Neuronopathic forms of GD can be associated with rapid neurological decline (Type II) or manifest as a chronic form (Type III) with a wide spectrum of neurological signs. Furthermore, there is now a well-established link between GBA1 mutations and Parkinson's disease (PD), with heterozygote mutations in GBA1 considered the commonest genetic defect in PD...
November 16, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27830583/dynamin-related-protein-1-drp1-mediating-mitophagy-contributes-to-the-pathophysiology-of-nervous-system-diseases-and-brain-injury
#9
REVIEW
Qiong Wu, Cheng-Liang Luo, Lu-Yang Tao
As the main source of energy (celluar ATP) in eukaryotic cells, mitochondria are involved in cellular physiology and pathology. The balance of mitochondrial dynamic, fission and fusion regulated by quality control mechanisms, provides a guarantee for maintaining mitochondrial function, even celluar function. Worn out mitochondria would be removed through mitophagy which is regulated by autophagy related proteins and mitochondrial membrane proteins. Drp1, dynamic-related protein 1, is regarded as one of the most important proteins to evaluate mitochondrial fission mediating mitophagy in neurodegenerative diseases (eg...
November 10, 2016: Histology and Histopathology
https://www.readbyqxmd.com/read/27829998/the-effects-and-mechanism-of-estrogen-on-rats-with-parkinson-s-disease-in-different-age-groups
#10
Xue-Zhong Li, Chen-Yan Sui, Qiang Chen, Yuan-Su Zhuang, Hong Zhang, Xiao-Ping Zhou
OBJECTIVE: In order to investigate the effect and mechanism of estrogen in rotenone-induced Parkinson's disease (PD) rats in different age groups. METHODS: we established rat models of PD by rotenone at different interventions. Then, behavioral tests, immunohistochemistry, western blot, high-performance liquid chromatography-electrochemical detector (HPLC-ECD) and electron microscopy were performed. RESULTS: Results revealed the following: (1) Rotenone significantly reduced rotarod latencies in senile rats, prolonged their climbing pole time, and decreased TH positive cells, DA and its metabolite, DOPAC...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27822367/dysregulation-of-autophagy-and-mitochondrial-function-in-parkinson-s-disease
#11
REVIEW
Bao Wang, Neeta Abraham, Guodong Gao, Qian Yang
Parkinson's disease (PD) is the second most common neurodegenerative disease. Increasing evidence supports that dysregulation of autophagy and mitochondrial function are closely related with PD pathogenesis. In this review, we briefly summarized autophagy pathway, which consists of macroautophagy, microautophagy and chaperone-mediated autophagy (CMA). Then, we discussed the involvement of mitochondrial dysfunction in PD pathogenesis. We specifically reviewed the recent developments in the relationship among several PD related genes, autophagy and mitochondrial dysfunction, followed by the therapeutic implications of these pathways...
2016: Translational Neurodegeneration
https://www.readbyqxmd.com/read/27818354/prolyl-oligopeptidase-inhibition-attenuates-the-toxicity-of-a-proteasomal-inhibitor-lactacystin-in-the-alpha-synuclein-overexpressing-cell-culture
#12
Timo T Myöhänen, Susanna Norrbacka, Mari H Savolainen
Lewy bodies, the histopathological hallmarks of Parkinson's disease (PD), contain insoluble and aggregated α-synuclein (aSyn) and many other proteins, proposing a role for failure in protein degradation system in the PD pathogenesis. Proteasomal dysfunction has indeed been linked to PD and aSyn oligomers have been shown to inhibit proteasomes and autophagy. Our recent studies have shown that inhibitors of prolyl oligopeptidase (PREP) can prevent the aggregation and enhance the clearance of accumulated aSyn, and therefore, we wanted to study if PREP inhibition can overcome the aSyn aggregation and toxicity induced by lactacystin, a proteasomal inhibitor...
November 3, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/27813607/inhibition-of-atg6-and-pi3k59f-autophagy-genes-in-neurons-decreases-lifespan-and-locomotor-ability-in-drosophila-melanogaster
#13
P G M'Angale, B E Staveley
Autophagy is a cellular mechanism implicated in the pathology of Parkinson's disease. The proteins Atg6 (Beclin 1) and Pi3K59F are involved in autophagosome formation, a key step in the initiation of autophagy. We first used the GMR-Gal4 driver to determine the effect of reducing the expression of the genes encoding these proteins on the developing Drosophila melanogaster eye. Subsequently, we inhibited their expression in D. melanogaster neurons under the direction of a Dopa decarboxylase (Ddc) transgene, and examined the effects on longevity and motor function...
October 24, 2016: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/27810402/impact-of-intermittent-fasting-on-health-and-disease-processes
#14
REVIEW
Mark P Mattson, Valter D Longo, Michelle Harvie
Humans in modern societies typically consume food at least three times daily, while laboratory animals are fed ad libitum. Overconsumption of food with such eating patterns often leads to metabolic morbidities (insulin resistance, excessive accumulation of visceral fat, etc.), particularly when associated with a sedentary lifestyle. Because animals, including humans, evolved in environments where food was relatively scarce, they developed numerous adaptations that enabled them to function at a high level, both physically and cognitively, when in a food-deprived/fasted state...
October 31, 2016: Ageing Research Reviews
https://www.readbyqxmd.com/read/27774335/n-acetylcysteine-in-combination-with-igf-1-enhances-neuroprotection-against-proteasome-dysfunction-induced-neurotoxicity-in-sh-sy5y-cells
#15
Benxu Cheng, Pinki Anand, Anxiu Kuang, Feroz Akhtar, Virginia L Scofield
Ubiquitin proteasome system (UPS) dysfunction has been implicated in the development of many neuronal disorders, including Parkinson's disease (PD). Previous studies focused on individual neuroprotective agents and their respective abilities to prevent neurotoxicity following a variety of toxic insults. However, the effects of the antioxidant N-acetylcysteine (NAC) on proteasome impairment-induced apoptosis have not been well characterized in human neuronal cells. The aim of this study was to determine whether cotreatment of NAC and insulin-like growth factor-1 (IGF-1) efficiently protected against proteasome inhibitor-induced cytotoxicity in SH-SY5Y cells...
2016: Parkinson's Disease
https://www.readbyqxmd.com/read/27769241/therapeutic-effect-of-berberine-on-tdp-43-related-pathogenesis-in-ftld-and-als
#16
Cheng-Fu Chang, Yi-Chao Lee, Kuen-Haur Lee, Hui-Ching Lin, Chia-Ling Chen, Che-Kun James Shen, Chi-Chen Huang
BACKGROUND: In the central nervous system regions of the sporadic and familial FTLD and ALS patients, TDP-43 has been identified as the major component of UBIs inclusions which is abnormally hyperphosphorylated, ubiquitinated, and cleaved into C-terminal fragments to form detergent-insoluble aggregates. So far, the effective drugs for FTLD and ALS neurodegenerative diseases are yet to be developed. Autophagy has been demonstrated as the major metabolism route of the pathological TDP-43 inclusions, hence activation of autophagy is a potential therapeutic strategy for TDP-43 pathogenesis in FTLD and ALS...
October 21, 2016: Journal of Biomedical Science
https://www.readbyqxmd.com/read/27742410/baicalein-attenuates-%C3%AE-synuclein-aggregation-inflammasome-activation-and-autophagy-in-the-mpp-treated-nigrostriatal-dopaminergic-system-in-vivo
#17
Kai-Chih Hung, Hui-Ju Huang, Yi-Ting Wang, Anya Maan-Yuh Lin
ETHNOPHARMACOLOGICAL RELEVANCE: Neuroinflammation, oxidative stress, and protein aggregation form a vicious cycle in the pathophysiology of Parkinson's disease (PD); activated microglia is the main location of neuroinflammation. A Chinese medicine book, "Shanghan Lun", known as the "Treatises on Cold damage Diseases" has suggested that Scutellaria baicalensis Georgi is effective in treating CNS diseases. The anti-inflammatory mechanisms of baicalein, a phenolic flavonoid in the dried root of Scutellaria baicalensis Georgi, remain to be explored...
October 11, 2016: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/27717584/parkinson-s-disease-snca-park2-and-lrrk2-targeting-micrornas-elevated-in-cingulate-gyrus
#18
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
https://www.readbyqxmd.com/read/27714635/mitochondria-associated-membranes-mams-overview-and-its-role-in-parkinson-s-disease
#19
M Rodríguez-Arribas, S M S Yakhine-Diop, J M Bravo-San Pedro, P Gómez-Suaga, R Gómez-Sánchez, G Martínez-Chacón, J M Fuentes, R A González-Polo, M Niso-Santano
Mitochondria-associated membranes (MAMs) are structures that regulate physiological functions between endoplasmic reticulum (ER) and mitochondria in order to maintain calcium signaling and mitochondrial biogenesis. Several proteins located in MAMs, including those encoded by PARK genes and some of neurodegeneration-related proteins (huntingtin, presenilin, etc.), ensure this regulation. In this regard, MAM alteration is associated with neurodegenerative diseases such as Parkinson's (PD), Alzheimer's (AD), and Huntington's diseases (HD) and contributes to the appearance of the pathogenesis features, i...
October 6, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27702699/targeting-chaperones-heat-shock-factor-1-and-unfolded-protein-response-promising-therapeutic-approaches-for-neurodegenerative-disorders
#20
Shambhunath Bose, Jungsook Cho
Protein misfolding, which is known to cause several serious diseases, is an emerging field that addresses multiple therapeutic areas. Misfolding of a disease-specific protein in the central nervous system ultimately results in the formation of toxic aggregates that may accumulate in the brain, leading to neuronal cell death and dysfunction, and associated clinical manifestations. A large number of neurodegenerative diseases in humans, including Alzheimer's, Parkinson's, Huntington's, and prion diseases, are primarily caused by protein misfolding and aggregation...
October 1, 2016: Ageing Research Reviews
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