keyword
MENU ▼
Read by QxMD icon Read
search

parkinson's disease and autophagy

keyword
https://www.readbyqxmd.com/read/28229934/novel-and-functional-atg12-gene-variants-in-sporadic-parkinson-s-disease
#1
Yuequn Li, Jian Huang, Shuchao Pang, Haihua Wang, Aimei Zhang, Robert G Hawley, Bo Yan
Parkinson's disease (PD) is a common and progressive neurodegenerative disease, including familial and sporadic cases. To date, genetic causes for sporadic PD, majority of PD cases, remain largely unknown. Accumulating evidence indicates that dysfunctional autophagy, a highly conserved cellular process, is involved in the PD pathogenesis. We speculated that changed expression levels of autophagy-related genes (ATG) may contribute to PD development. Previously, we have genetically analyzed ATG5 and ATG7 genes in sporadic PD patients and identified several functional DNA sequence variants (DSVs)...
February 13, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28223210/a-novel-glp-1-gip-dual-receptor-agonist-protects-from-6-ohda-lesion-in-a-rat-model-of-parkinson-s-disease
#2
Jaishree Jalewa, Mohit Kumar Sharma, Simon Gengler, Christian Hölscher
The incretins glucagon-like peptide 1 (GLP-1) and glucose dependent insulinotropic polypeptide (GIP) are growth factors that have shown neuroprotective effects in animal models of Parkinson's and Alzheimer's disease. In addition, the GLP-1 mimetic exendin-4 has shown protective effects in a clinical trial in Parkinson's disease (PD) patients. GLP-1 analogues are currently on the market as treatments for type II diabetes. We previously showed that the novel dual agonist (DA-JC1) was effective in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD...
February 20, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28205624/the-small-molecule-auten-99-autophagy-enhancer-99-prevents-the-progression-of-neurodegenerative-symptoms
#3
Tibor Kovács, Viktor Billes, Marcell Komlós, Bernadette Hotzi, Anna Manzéger, Anna Tarnóci, Diána Papp, Fanni Szikszai, Janka Szinyákovics, Ákos Rácz, Béla Noszál, Szilvia Veszelka, Fruzsina R Walter, Mária A Deli, Laszlo Hackler, Robert Alfoldi, Orsolya Huzian, Laszlo G Puskas, Hanna Liliom, Krisztián Tárnok, Katalin Schlett, Adrienn Borsy, Ervin Welker, Attila L Kovács, Zsolt Pádár, Attila Erdős, Adam Legradi, Annamaria Bjelik, Károly Gulya, Balázs Gulyás, Tibor Vellai
Autophagy functions as a main route for the degradation of superfluous and damaged constituents of the cytoplasm. Defects in autophagy are implicated in the development of various age-dependent degenerative disorders such as cancer, neurodegeneration and tissue atrophy, and in accelerated aging. To promote basal levels of the process in pathological settings, we previously screened a small molecule library for novel autophagy-enhancing factors that inhibit the myotubularin-related phosphatase MTMR14/Jumpy, a negative regulator of autophagic membrane formation...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28202669/the-lrrk2-macroautophagy-axis-and-its-relevance-to-parkinson-s-disease
#4
REVIEW
Claudia Manzoni
A wide variety of different functions and an impressive array of interactors have been associated with leucine-rich repeat kinase 2 (LRRK2) over the years. Here, I discuss the hypothesis that LRRK2 may be capable of interacting with different proteins at different times and places, therefore, controlling a plethora of diverse functions based on the different complexes formed. Among these, I will then focus on macroautophagy in the general context of the endolysosomal system. First, the relevance of autophagy in Parkinson's disease will be evaluated giving a brief overview of all the relevant Parkinson's disease genes; then, the association of LRRK2 with macroautophagy and the endolysosomal pathway will be analyzed based on the supporting literature...
February 8, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28197072/hmgb1-mediates-autophagy-dysfunction-via-perturbing-beclin1-vps34-complex-in-dopaminergic-cell-model
#5
Jinsha Huang, Jiaolong Yang, Yan Shen, Haiyang Jiang, Chao Han, Guoxin Zhang, Ling Liu, Xiaoyun Xu, Jie Li, Zhicheng Lin, Nian Xiong, Zhentao Zhang, Jing Xiong, Tao Wang
Parkinson's disease (PD), a progressive neurodegenerative disorder, is characterized by irreversible dopaminergic neuron loss and intra-neuronal α-synuclein aggregation. High mobility group box 1 (HMGB1) has been proven to be involved in autophagy dysfunction induced by α-synuclein accumulation, and the Beclin1-vacuolar protein sorting 34 (Vps34) complex is of great importance to the initiation of autophagy. Nevertheless, the concrete interaction mechanism between HMGB1, α-synuclein and autophagy remains elusive, especially in the context of PD...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28186670/rab7-may-be-a-novel-therapeutic-target-for-neurologic-diseases-as-a-key-regulator-in-autophagy
#6
REVIEW
Haixia Wen, Lixuan Zhan, Siyuan Chen, Long Long, En Xu
Macroautophagy is an evolutionally conserved membrane trafficking pathway that delivers intracellular materials to lysosomes for degradation and recycling. Rab7, as a member of the Rab GTPase superfamily, has a unique role in the regulation of macroautophagy, especially in modulating autophagy flux. The functional states of Rab7 generally switch between GTP-bound and GDP-bound states under the control of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). Activated GTP-Rab7 is capable of regulating autophagosome formation, autophagosome transportation along microtubules, endosome and autophagosome maturation, as well as lysosome biogenesis via interacting with its effector molecules...
February 10, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28168579/lrrk2-an-emerging-new-molecule-in-the-enteric-neuronal-system-that-quantitatively-regulates-neuronal-peptides-and-iga-in-the-gut
#7
Tatsunori Maekawa, Hitomi Shimayama, Hiromichi Tsushima, Fumitaka Kawakami, Rei Kawashima, Makoto Kubo, Takafumi Ichikawa
BACKGROUND: Leucine-rich repeat kinase 2 (LRRK2) is a recently discovered molecule associated with familial and sporadic Parkinson's disease. It regulates many central neuronal functions such as cell proliferation, apoptosis, autophagy, and axonal extension. However, in contrast to the well-documented function of LRRK2 in central neurons, it is unclear whether LRRK2 is expressed in enteric neurons and affects the physiology of the gut. AIMS: By examining LRRK2-KO mice, this study investigated whether enteric neurons express LRRK2 and whether intestinal neuronal peptides and IgA are quantitatively changed...
February 6, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28168426/mitochondrial-metabolism-regulates-microtubule-acetylome-and-autophagy-trough-sirtuin-2-impact-for-parkinson-s-disease
#8
Ana R Esteves, Daniela M Arduíno, Diana F Silva, Sofia D Viana, Frederico C Pereira, Sandra M Cardoso
Alterations in microtubule-dependent transport, mitochondrial dysfunction, and autophagic pathology are involved in neurodegeneration observed in sporadic Parkinson's disease. However, the mechanistic link connecting these events remains elusive. We observed that NAD(+) metabolism is altered in sporadic Parkinson's disease patient-derived cells, which contributes to Sirtuin-2 activation and subsequent decrease in acetylated-α-tubulin levels. Pharmacological inhibition of sirtuin-2 deacetylase activity selectively enhanced α-tubulin acetylation and facilitated the trafficking and clearance of misfolded proteins...
February 6, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28138322/iron-deposition-leads-to-neuronal-%C3%AE-synuclein-pathology-by-inducing-autophagy-dysfunction
#9
Wenbin Wan, Lirong Jin, Zigao Wang, Lingyan Wang, Guoqiang Fei, Fanlong Ye, Xiaoli Pan, Changpeng Wang, Chunjiu Zhong
Growing evidence has indicated that iron deposition in the substantia nigra plays an important role in Parkinson's disease (PD). However, the underlying mechanism is still elusive. Using primary dopaminergic neurons and SH-SY5Y cells cultured in vitro, we observed that iron loading increased α-synuclein and reactive oxygen species (ROS) levels in these cells but did not affect the intracellular α-synuclein mRNA levels. Furthermore, iron loading significantly downregulated Beclin-1 levels and decreased the ratio of microtubule-associated protein 1 light chain 3 isoforms (LC3 II/LC3 I)...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28137648/autophagic-modulation-by-rosuvastatin-prevents-rotenone-induced-neurotoxicity-in-an-in-vitro-model-of-parkinson-s-disease
#10
Seo Young Kang, Sang-Bin Lee, Hee Ju Kim, Hee-Tae Kim, Hyun Ok Yang, Wooyoung Jang
Statins have been reported to have neuroprotective effects through anti-oxidant, anti-apoptotic, and anti-inflammatory mechanisms, and statin can also modulate autophagic signaling in an oxygen-toxicity models. Therefore, we investigated the effects of statin on autophagy markers and evaluated the neuroprotective effect of rosuvastatin against rotenone-induced neurotoxicity. As an in vitro model of Parkinson's disease(PD) we adopted the rotenone-induced neurotoxicity model in SH-SY5Y cells. Cell viability was measured using the MTT assay, and to detect the expression of LC3 and α-synuclein, immunofluorescence analysis was performed...
March 6, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28122627/therapeutic-potential-of-autophagy-enhancing-agents-in-parkinson-s-disease
#11
REVIEW
Tim E Moors, Jeroen J M Hoozemans, Angela Ingrassia, Tommaso Beccari, Lucilla Parnetti, Marie-Christine Chartier-Harlin, Wilma D J van de Berg
Converging evidence from genetic, pathological and experimental studies have increasingly suggested an important role for autophagy impairment in Parkinson's Disease (PD). Genetic studies have identified mutations in genes encoding for components of the autophagy-lysosomal pathway (ALP), including glucosidase beta acid 1 (GBA1), that are associated with increased risk for developing PD. Observations in PD brain tissue suggest an aberrant regulation of autophagy associated with the aggregation of α-synuclein (α-syn)...
January 25, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28115417/the-parkinson-s-disease-linked-protein-tmem230-is-required-for-rab8a-mediated-secretory-vesicle-trafficking-and-retromer-trafficking
#12
Myung Jong Kim, Han-Xiang Deng, Yvette C Wong, Teepu Siddique, Dimitri Krainc
TMEM230 is a newly identified Parkinson's disease (PD) gene encoding a transmembrane protein whose cellular and pathogenic roles remain largely unknown. Here, we demonstrate that loss of TMEM230 disrupts retromer cargo CI-M6PR (cation-independent mannose 6-phosphate receptor) trafficking and autophagic cargo degradation rates. TMEM230 depletion further inhibits extracellular secretion of the autophagic cargo p62 and immature lysosomal hydrolases in Golgi-derived vesicles leading to their intracellular accumulation, and is specifically mediated by loss of the small GTPase Rab8a...
January 22, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28109117/lipid-profiling-of-parkin-mutant-human-skin-fibroblasts
#13
Simona Lobasso, Paola Tanzarella, Daniele Vergara, Michele Maffia, Tiziana Cocco, Angela Corcelli
Parkin mutations are a major cause of early-onset Parkinson's disease (PD). The impairment of protein quality control system together with defects in mitochondria and autophagy process are consequences of the lack of parkin, which leads to neurodegeneration. Little is known about the role of lipids in these alterations of cell functions. In the present study, parkin-mutant human skin primary fibroblasts have been considered as cellular model of PD to investigate on possible lipid alterations associated with the lack of parkin protein...
January 21, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28099881/mesencephalic-astrocyte-derived-neurotrophic-factor-alleviated-6-ohda-induced-cell-damage-via-ros-ampk-mtor-mediated-autophagic-inhibition
#14
Jingxing Zhang, Qiong Cai, Ming Jiang, Yigang Liu, Hua Gu, Jia Guo, Hui Sun, Jianmin Fang, Lingjing Jin
Autophagy and apoptosis are commonly involved in the dopaminergic neuron damage in the pathogenesis of Parkinson's disease. Recently, the autophagy pathway is thought to be critical to the process of PD. Therefore, the regulation of autophagy may be a potential strategy for PD treatment. Mesencephalic astrocyte-derived neurotrophic factor (MANF) has been reported to have neuroprotective effects through anti-apoptosis, anti-oxidative, and anti-inflammatory mechanisms in PD. In this study, we investigated the role of autophagy system in MANF-mediated neuroprotection against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity...
January 15, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28068606/trehalose-does-not-improve-neuronal-survival-on-exposure-to-alpha-synuclein-pre-formed-fibrils
#15
Matthew Redmann, Willayat Y Wani, Laura Volpicelli-Daley, Victor Darley-Usmar, Jianhua Zhang
Parkinson's disease is a debilitating neurodegenerative disorder that is pathologically characterized by intracellular inclusions comprised primarily of alpha-synuclein (αSyn) that can also be transmitted from neuron to neuron. Several lines of evidence suggest that these inclusions cause neurodegeneration. Thus exploring strategies to improve neuronal survival in neurons with αSyn aggregates is critical. Previously, exposure to αSyn pre-formed fibrils (PFFs) has been shown to induce aggregation of endogenous αSyn resulting in cell death that is exacerbated by either starvation or inhibition of mTOR by rapamycin, both of which are able to induce autophagy, an intracellular protein degradation pathway...
April 2017: Redox Biology
https://www.readbyqxmd.com/read/28057299/mechanisms-of-parkinson-s-disease-lessons-from-drosophila
#16
V L Hewitt, A J Whitworth
The power of Drosophila genetics has attracted attention in tackling important biomedical challenges such as the understanding and prevention of neurodegenerative diseases. Parkinson's disease (PD) is the most common neurodegenerative movement disorder which results from the relentless degeneration of midbrain dopaminergic neurons. Over the past two decades tremendous advances have been made in identifying genes responsible for inherited forms of PD. The ease of genetic manipulation in Drosophila has spurred the development of numerous models of PD, including expression of human genes carrying pathogenic mutations or the targeted mutation of conserved orthologs...
2017: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/28055011/neuronal-hemoglobin-affects-dopaminergic-cells-response-to-stress
#17
Marta Codrich, Maria Bertuzzi, Roberta Russo, Margherita Francescatto, Stefano Espinoza, Lorena Zentilin, Mauro Giacca, Daniela Cesselli, Antonio Paolo Beltrami, Paolo Ascenzi, Silvia Zucchelli, Francesca Persichetti, Giampiero Leanza, Stefano Gustincich
Hemoglobin (Hb) is the major protein in erythrocytes and carries oxygen (O2) throughout the body. Recently, Hb has been found synthesized in atypical sites, including the brain. Hb is highly expressed in A9 dopaminergic (DA) neurons of the substantia nigra (SN), whose selective degeneration leads to Parkinson's disease (PD). Here we show that Hb confers DA cells' susceptibility to 1-methyl-4-phenylpyridinium (MPP(+)) and rotenone, neurochemical cellular models of PD. The toxic property of Hb does not depend on O2 binding and is associated with insoluble aggregate formation in the nucleolus...
January 5, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28017782/parkin-and-pink1-functions-in-oxidative-stress-and-neurodegeneration
#18
Sandeep K Barodia, Rose B Creed, Matthew S Goldberg
Loss-of-function mutations in the genes encoding Parkin and PINK1 are causally linked to autosomal recessive Parkinson's disease (PD). Parkin, an E3 ubiquitin ligase, and PINK1, a mitochondrial-targeted kinase, function together in a common pathway to remove dysfunctional mitochondria by autophagy. Presumably, deficiency for Parkin or PINK1 impairs mitochondrial autophagy and thereby increases oxidative stress due to the accumulation of dysfunctional mitochondria that release reactive oxygen species. Parkin and PINK1 likely have additional functions that may be relevant to the mechanisms by which mutations in these genes cause neurodegeneration, such as regulating inflammation, apoptosis, or dendritic morphogenesis...
December 22, 2016: Brain Research Bulletin
https://www.readbyqxmd.com/read/27983596/estrogenic-endocrine-disrupting-chemicals-influencing-nrf1-regulated-gene-networks-in-the-development-of-complex-human-brain-diseases
#19
REVIEW
Mark Preciados, Changwon Yoo, Deodutta Roy
During the development of an individual from a single cell to prenatal stages to adolescence to adulthood and through the complete life span, humans are exposed to countless environmental and stochastic factors, including estrogenic endocrine disrupting chemicals. Brain cells and neural circuits are likely to be influenced by estrogenic endocrine disruptors (EEDs) because they strongly dependent on estrogens. In this review, we discuss both environmental, epidemiological, and experimental evidence on brain health with exposure to oral contraceptives, hormonal therapy, and EEDs such as bisphenol-A (BPA), polychlorinated biphenyls (PCBs), phthalates, and metalloestrogens, such as, arsenic, cadmium, and manganese...
December 13, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27956235/valproic-acid-protects-against-mpp-mediated-neurotoxicity-in-sh-sy5y-cells-through-autophagy
#20
Y Zhang, J Y Wu, L H Weng, X X Li, L J Yu, Y Xu
Autophagy is a common physiological activity in cells. Studies show that dysregulation of autophagy is involved in the pathogenesis of Parkinson's disease (PD). As a commonly used anti-epileptic drug, valproic acid (VPA) has shown neuroprotective effects in PD. The aim of this study was to explore whether the autophagy induced by VPA involved in the neuroprotective effects in PD cell model. We found that VPA treatment counteracted MPP(+)-caused autophagic flux impairment. Forthermore, VPA could alleviates apoptosis, reduce reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP) loss caused by MPP(+)...
December 9, 2016: Neuroscience Letters
keyword
keyword
44212
1
2
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"