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https://www.readbyqxmd.com/read/28820063/loss-in-toxic-function-of-aggregates-of-%C3%AE-synuclein-mutants-by-a-%C3%AE-synuclein-derived-peptide
#1
Soheila Mohammadi, Maryam Nikkhah, Saman Hosseinkhani
Parkinson's disease (PD) primarily results from a severe and selective damage of dopaminergic neurons. The neuropathological hallmark of the disease is the presence of inclusions known as Lewy bodies, that are enriched in α-Synuclein (αS) nanofibrils, within the surviving neurons. The inhibition of αS aggregation is considered as an efficient approach for preventing or treating PD. To date, several researchers have been focused on screening for the inhibitors that are able to block, slow down, or reverse αS aggregation, particularly at its early stages...
August 18, 2017: Protein and Peptide Letters
https://www.readbyqxmd.com/read/28810585/glutamine-promotes-hsp70-and-inhibits-%C3%AE-synuclein-accumulation-in-pheochromocytoma-pc12-cells
#2
Haiyang Wang, Chongyang Tang, Zhenfeng Jiang, Xiao Zhou, Jianhang Chen, Meng Na, Hong Shen, Zhiguo Lin
Hsp70 regulates α-Synuclein (α-Syn) degeneration in Parkinson's disease (PD), indicating that Hsp70 promotion may be able to prevent or reverse α-Syn-induced toxicity in PD. Additionally, it has been demonstrated that glutamine (Gln) enhances Hsp70 expression. In the present study, Gln-induced Hsp70 promotion in pheochromocytoma was investigated with reverse transcription- quantitative polymerase chain reaction and western blotting methods. Then it was observed whether heat shock factor (HSF)-1 was required for this phenomenon with an RNA interference strategy...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28807675/substantial-protection-against-mptp-associated-parkinson-s-neurotoxicity-in-vitro-and-in-vivo-by-anti-cancer-agent-su4312-via-activation-of-mef2d-and-inhibition-of-mao-b
#3
Baojian Guo, Shengquan Hu, Chengyou Zheng, Hongyu Wang, Fangcheng Luo, Haitao Li, Wei Cui, Xifei Yang, Guozhen Cui, Shinghung Mak, Tony Chung-Lit Choi, Edmond Dik-Lung Ma, Yuqiang Wang, Simon Ming Yuen Lee, Zaijun Zhang, Yifan Han
We have previously demonstrated the unexpected neuroprotection of the anti-cancer agent SU4312 in cellular models associated with Parkinson's disease (PD). However, the precise mechanisms underlying its neuroprotection are still unknown, and the effects of SU4312 on rodent models of PD have not been characterized. In the current study, we found that the protection of SU4312 against 1-methyl-4-phenylpyridinium ion (MPP(+))-induced neurotoxicity in PC12 cells was achieved through the activation of transcription factor myocyte enhancer factor 2D (MEF2D), as evidenced by the fact that SU4312 stimulated myocyte enhancer factor 2 (MEF2) transcriptional activity and prevented the inhibition of MEF2D protein expression caused by MPP(+), and that short hairpin RNA (ShRNA)-mediated knockdown of MEF2D significantly abolished the neuroprotection of SU4312...
August 11, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28807673/gpr55-a-therapeutic-target-for-parkinson-s-disease
#4
Marta Celorrio, Estefanía Rojo-Bustamante, Diana Fernández-Suárez, Elena Sáez, Ander Estella-Hermoso de Mendoza, Christa E Müller, María J Ramírez, Julen Oyarzábal, Rafael Franco, María S Aymerich
The GPR55 receptor is expressed abundantly in the brain, especially in the striatum, suggesting it might fulfill a role in motor function. Indeed, motor behavior is impaired in mice lacking GPR55, which also display dampened inflammatory responses. Abnormal-cannabidiol (Abn-CBD), a synthetic cannabidiol (CBD) isomer, is a GPR55 agonist that may serve as a therapeutic agent in the treatment of inflammatory diseases. In this study, we explored whether modulating GPR55 could also represent a therapeutic approach for the treatment of Parkinson's disease (PD)...
August 12, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28805588/weight-in-parkinson-s-disease-phenotypical-significance
#5
Jagdish C Sharma, Anna Lewis
Body weight in Parkinson's disease (PD) is a significant nonmotor feature. Weight homeostasis is a complex physiological process and gets deranged in PD patients leading to changes in weight. While both the low and high body weight have been reported as risk factors for PD, the majority of PD patients have a lower weight and a subset of patients lose weight during the course of the disease, while a small proportion gain weight. A number of clinical parameters such as older age, impaired cognition, severity of disease, and an imbalance of food intake determined by satiety and hunger hormones have been reported to be associated with but not the cause of weight change...
2017: International Review of Neurobiology
https://www.readbyqxmd.com/read/28805584/constipation-in-parkinson-s-disease
#6
Fabrizio Stocchi, Margherita Torti
Constipation is one of the main and disabling nonmotor symptoms in Parkinson's disease (PD), with a prevalence ranging from 24.6% to 63% according to the different diagnostic criteria used to define chronic constipation. Constipation is currently recognized as a risk factor of PD in relation to the number of evacuation per week and its severity. Moreover, several studies have demonstrated that constipation may precede the occurrence of motor symptoms underlying an earlier involvement of the enteric nervous system and the dorsal motor nucleus of the vagus in the α-synuclein pathology...
2017: International Review of Neurobiology
https://www.readbyqxmd.com/read/28805572/personalized-medicine-and-nonmotor-symptoms-in-parkinson-s-disease
#7
Nataliya Titova, K Ray Chaudhuri
Parkinson's disease (PD) is a multineurotransmitter dysfunction related disorder resulting in a range of motor and nonmotor symptoms. Phenotypic heterogeneity is pronounced in PD and nonmotor symptoms dominant subtypes have been described. These endophenotypes may be underpinned by considerable nondopaminergic dysfunction; however, conventional treatment of PD continues to be mostly reliant on dopamine replacement strategy or manipulation of brain dopaminergic pathways. Consequently, treatment of many nondopaminergic nonmotor and some motor symptoms remains a key unmet need...
2017: International Review of Neurobiology
https://www.readbyqxmd.com/read/28805570/swallowing-dysfunctions-in-parkinson-s-disease
#8
Janine A Simons
Dysphagia is a very frequent and highly relevant symptom in Parkinson's disease (PD) for quality of life, morbidity, and remaining lifetime, which is unfortunately widely underdiagnosed and underestimated regarding patients' centered care. Especially in early stages, the causal association between disease and swallowing disabilities remains unnoticed, which may be accounted for by the inability of caregivers and physicians to detect subtle swallowing problems and by the low self-awareness among PD patients...
2017: International Review of Neurobiology
https://www.readbyqxmd.com/read/28805567/nutrition-and-nonmotor-symptoms-of-parkinson-s-disease
#9
Laurie K Mischley
To date, no guidelines exist for the screening, evaluation, and management of nutritional status in PD. Dozens of studies demonstrate an association between diet in adulthood with subsequent risk of developing PD. Individuals with PD are at increased risk of malnutrition due to the increased metabolic demands and disease pathophysiology. Risk of malnutrition is further complicated by anosmia, swallowing difficulties, constipation, and drug-nutrient interactions. An emerging body of evidence suggests that the intestinal tract is affected early in the disease, creating therapeutic opportunities for early intervention...
2017: International Review of Neurobiology
https://www.readbyqxmd.com/read/28802652/an-autophagic-mechanism-is-involved-in-the-6-hydroxydopamine-induced-neurotoxicity-in-vivo
#10
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/28801819/treadmill-exercise-prevents-increase-of-neuroinflammation-markers-involved-in-the-dopaminergic-damage-of-the-6-ohda-parkinson-s-disease-model
#11
Caroline Cristiano Real, Priscila Crespo Garcia, Luiz R G Britto
Parkinson's disease (PD) involves loss of dopaminergic neurons in the substantia nigra (SN), which can be correlated to neuroinflammatory changes with the aging of the nervous system. On the other hand, exercise can reduce the deleterious effects promoted by age, but the mechanism involved is still unclear. This study investigated the preventive exercise-induced changes on neuroinflammatory processes in a rat model of PD induced by unilateral striatal injections of 6-hydroxydopamine (6-OHDA). Adult male Wistar rats were divided into two groups: (1) sedentary (SED) or (2) exercised (EX), animals that did treadmill exercise three times per week, every other day, for 4 weeks prior to 6-OHDA or saline injection...
August 11, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28801614/palladium-nanoparticles-entrapped-in-a-self-supporting-nanoporous-gold-wire-as-sensitive-dopamine-biosensor
#12
Xin Yi, Yuxuan Wu, Guoxin Tan, Peng Yu, Lei Zhou, Zhengnan Zhou, Junqi Chen, Zhengao Wang, Jinshan Pang, Chengyun Ning
Traced dopamine (DA) detection is critical for the early diagnosis and prevention of some diseases such as Parkinson's, Alzheimer and schizophrenia. In this research, a novel self-supporting three dimensional (3D) bicontinuous nanoporous electrochemical biosensor was developed for the detection of dopamine by Differential Pulse Voltammetry (DPV). This biosensor was fabricated by electrodepositing palladium nanoparticles (Pd) onto self-supporting nanoporous gold (NPG) wire. Because of the synergistic effects of the excellent catalytic activity of Pd and novel structure of NPG wire, the palladium nanoparticles decorated NPG (Pd/NPG) biosensor possess tremendous superiority in the detection of DA...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28800639/mitochondrial-impairment-and-melatonin-protection-in-parkinsonian-mice-do-not-depend-of-inducible-or-neuronal-nitric-oxide-synthases
#13
Ana López, Francisco Ortiz, Carolina Doerrier, Carmen Venegas, Marisol Fernández-Ortiz, Paula Aranda, María E Díaz-Casado, Beatriz Fernández-Gil, Eliana Barriocanal-Casado, Germaine Escames, Luis C López, Darío Acuña-Castroviejo
MPTP-mouse model constitutes a well-known model of neuroinflammation and mitochondrial failure occurring in Parkinson's disease (PD). Although it has been extensively reported that nitric oxide (NO●) plays a key role in the pathogenesis of PD, the relative roles of nitric oxide synthase isoforms iNOS and nNOS in the nigrostriatal pathway remains, however, unclear. Here, the participation of iNOS/nNOS isoforms in the mitochondrial dysfunction was analyzed in iNOS and nNOS deficient mice. Our results showed that MPTP increased iNOS activity in substantia nigra and striatum, whereas it sharply reduced complex I activity and mitochondrial bioenergetics in all strains...
2017: PloS One
https://www.readbyqxmd.com/read/28792609/egcg-attenuates-fe-iii-induced-conformational-transition-of-%C3%AE-synuclein-and-protects-as-pc12-cells-against-fe-iii-induced-death
#14
Juan Zhao, Lihui Xu, Qingnan Liang, Qing Sun, Congheng Chen, Yuan Zhang, Yu Ding, Ping Zhou
The fibrillation and aggregation of α-synuclein (AS), along with the conformational transition from random coil to β-sheet, are the critical steps in the development of Parkinson's disease (PD). It is acknowledged that iron accumulation in the brain may lead to the fibrillation of AS. However, (-)-epigallocatechin gallate (EGCG) can penetrate the blood-brain barrier, chelate metal ions and inhibit the fibrillation of amyloid proteins. Therefore, EGCG is warranted to be investigated for its potential to cure amyloid-related diseases...
August 9, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28791420/melatonin-as-a-mitochondrial-protector-in-neurodegenerative-diseases
#15
REVIEW
Pawaris Wongprayoon, Piyarat Govitrapong
Mitochondria are crucial organelles as their role in cellular energy production of eukaryotes. Because the brain cells demand high energy for maintaining their normal activities, disturbances in mitochondrial physiology may lead to neuropathological events underlying neurodegenerative conditions such as Alzheimer's disease, Parkinson's disease and Huntington's disease. Melatonin is an endogenous compound with a variety of physiological roles. In addition, it possesses potent antioxidant properties which effectively play protective roles in several pathological conditions...
August 8, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28790012/mdivi-1-ameliorates-early-brain-injury-after-subarachnoid-hemorrhage-via-the-suppression-of-inflammation-related-blood-brain-barrier-disruption-and-endoplasmic-reticulum-stress-based-apoptosis
#16
Lin-Feng Fan, Ping-You He, Yu-Cong Peng, Qing-Hua Du, Yi-Jun Ma, Jian-Xiang Jin, Hang-Zhe Xu, Jian-Ru Li, Zhi-Jiang Wang, Sheng-Long Cao, Tao Li, Feng Yan, Chi Gu, Lin Wang, Gao Chen
Aberrant modulation of mitochondrial dynamic network, which shifts the balance of fusion and fission towards fission, is involved in brain damage of various neurodegenerative diseases including Parkinson's disease, Huntington's disease and Alzheimer's disease. A recent research has shown that the inhibition of mitochondrial fission alleviates early brain injury after experimental subarachnoid hemorrhage, however, the underlying molecular mechanisms have remained to be elucidated. This study was undertaken to characterize the effects of the inhibition of dynamin-related protein-1 (Drp1, a dominator of mitochondrial fission) on blood-brain barrier (BBB) disruption and neuronal apoptosis following SAH and the potential mechanisms...
August 5, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28782414/protective-effect-of-neuropeptide-apelin-13-on-6-hydroxydopamine-induced-neurotoxicity-in-sh-sy5y-dopaminergic-cells-involvement-of-its-antioxidant-and-antiapoptotic-properties
#17
Elham Pooresmaeili-Babaki, Saeed Esmaeili-Mahani, Mehdi Abbasnejad, Hadi Ravan
Parkinson's disease (PD) is a severe neurodegenerative disorder characterized by the loss of brain dopaminergic neurons. Beside pharmacologic and symptomatic treatment of PD the neuroprotective therapy has recently attracted more attention. Apelin, a novel neuropeptide, and its receptors have numerous reported roles in regulating brain functions. In addition, this peptide has potent neuroprotective effects in some neurodegenerative situations. Here, the effects of apelin-13 were investigated in a cell model of PD...
August 7, 2017: Rejuvenation Research
https://www.readbyqxmd.com/read/28781200/outcome-of-gastrostomy-in-parkinsonism-a-retrospective-study
#18
Clémence Marois, Maria Del Mar Amador, Christine Payan, Lucette Lacomblez, Anne-Marie Bonnet, Bertrand Degos, Jean-Christophe Corvol, Marie Vidailhet, Nadine Le Forestier, Valérie Mesnage, David Grabli
OBJECTIVE: To investigate the indications and the outcomes of gastrostomy tube insertion in patients with parkinsonian syndromes. METHODS: Consecutive patients with Parkinson's disease or atypical parkinsonism, seen in two French tertiary referral movement disorders centers, that received gastrostomy tube insertion (GTI) for feeding between 2008 and 2014 were included in this retrospective study. Data regarding clinical status, indications and outcomes were retrieved from medical files...
June 23, 2017: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/28770670/potential-repositioning-of-exemestane-as-a-neuroprotective-agent-for-parkinson-s-disease
#19
Hyo Jin Son, Se Hee Han, Ji Ae Lee, Eun Jung Shin, Onyou Hwang
Parkinson's disease (PD) is a neurodegenerative disorder characterised by selective degeneration of the nigral dopaminergic neurons, and neuroinflammation and oxidative stress are believed to be involved in its pathogenesis. In the present study, we provide data that the synthetic steroid exemestane, which is currently being used to treat breast cancer, may be useful for PD therapy. In BV-2 microglial cells, exemestane activated the transcription factor Nrf2 and induced expression of the Nrf2-dependent genes that encode the antioxidant enzymes NAD(P)H: quinone oxidoreductase 1, haem oxygenase-1, and glutamylcysteine ligase...
June 2017: Free Radical Research
https://www.readbyqxmd.com/read/28764903/achieving-neuroprotection-with-lrrk2-kinase-inhibitors-in-parkinson-disease
#20
REVIEW
Andrew B West
In the translation of discoveries from the laboratory to the clinic, the track record in developing disease-modifying therapies in neurodegenerative disease is poor. A carefully designed development pipeline built from discoveries in both pre-clinical models and patient populations is necessary to optimize the chances for success. Genetic variation in the leucine-rich repeat kinase two gene (LRRK2) is linked to Parkinson disease (PD) susceptibility. Pathogenic mutations, particularly those in the LRRK2 GTPase (Roc) and COR domains, increase LRRK2 kinase activities in cells and tissues...
July 29, 2017: Experimental Neurology
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