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Parkinson's disease and neuroprotection

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https://www.readbyqxmd.com/read/28106982/a-novel-iron-ii-preferring-dopamine-agonist-chelator-as-potential-symptomatic-and-neuroprotective-therapeutic-agent-for-parkinson-s-disease
#1
Banibrata Das, Ashoka Kandegedara, Liping Xu, Tamara Antonio, Timothy L Stemmler, Maarten E A Reith, Aloke K Dutta
Parkinson's disease (PD) is a progressive neurodegenerative disorder and development of disease-modifying treatment is still an unmet medical need. Considering the implication of free iron (II) in PD, we report here the design and characterization of a novel hybrid iron chelator, (-)-12 (D-607) as a multitarget-directed ligand against PD. Binding and functional assays at dopamine D2/D3 receptors indicate potent agonist activity of (-)-12. The molecule displayed an efficient preferential iron (II) chelation properties along with potent in vivo activity in a reserpinized PD animal model...
January 20, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28106099/nesfatin-1-protects-dopaminergic-neurons-against-mpp-mptp-induced-neurotoxicity-through-the-c-raf-erk1-2-dependent-anti-apoptotic-pathway
#2
Xiao-Li Shen, Ning Song, Xi-Xun Du, Yong Li, Jun-Xia Xie, Hong Jiang
Several brain-gut peptides have been reported to have a close relationship with the central dopaminergic system; one such brain-gut peptide is nesfatin-1. Nesfatin-1 is a satiety peptide that is predominantly secreted by X/A-like endocrine cells in the gastric glands, where ghrelin is also secreted. We previously reported that ghrelin exerted neuroprotective effects on nigral dopaminergic neurons, which implied a role for ghrelin in Parkinson's disease (PD). In the present study, we aim to clarify whether nesfatin-1 has similar effects on dopaminergic neurons both in vivo and in vitro...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28100851/effects-of-propofol-on-oxidative-stress-parameters-in-selected-parts-of-the-brain-in-a-rat-model-of-parkinson-disease
#3
Ewa Romuk, Wioletta Szczurek, Przemysław Nowak, Marta Skowron, Bernard Prudel, Edyta Hudziec, Ewa Chwalińska, Ewa Birkner
INTRODUCTION: Propofol is an intravenous sedative-hypnotic agent that is commonly used to induce and maintain general anaesthesia. This drug has antioxidant properties, which are partly caused by a phenolic structure similar to α-tocopherol. The present study aimed to evaluate the effect of propofol on the level of oxidative stress biomarkers in the frontal cortex, striatum, thalamus, hippocampus and cerebellum in rats with experimental Parkinson's disease (PD). MATERIAL/METHODS: The experiment was performed on 24 male Wistar rats assigned to the following groups: 1 - control; 2 - PD; 3 - PD with propofol...
December 31, 2016: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28099881/mesencephalic-astrocyte-derived-neurotrophic-factor-alleviated-6-ohda-induced-cell-damage-via-ros-ampk-mtor-mediated-autophagic-inhibition
#4
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/28096964/g-csf-for-mobilizing-transplanted-bone-marrow-stem-cells-in-rat-model-of-parkinson-s-disease
#5
Manouchehr Safari, Behnaz Jafari, Sam Zarbakhsh, Hamidreza Sameni, Abbas Ali Vafaei, Nasrin Khan Mohammadi, Laya Ghahari
OBJECTIVES: Granulocyte-colony stimulating factor (G-CSF) is used in clinical practice for the treatment of neutropenia and to stimulate generation of hematopoietic stem cells in bone marrow donors. In the present study, the ability of G-CSF in mobilizing exogenous bone marrow stem cells (BMSCs) from peripheral blood into the brain was tested. We for the first time injected a small amount of BMSCs through the tail vein. MATERIALS AND METHODS: We choose 25 male Wistar rats (200-250 g) were lesioned by 6-OHDA injected into the left substantia nigra, pars compacta (SNpc)...
December 2016: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/28096960/estrogen-agonist-genistein-differentially-influences-the-cognitive-and-motor-disorders-in-an-ovariectomized-animal-model-of-parkinsonism
#6
Elaheh Arbabi, Gholamali Hamidi, Sayyed Alireza Talaei, Mahmoud Salami
OBJECTIVES: Parkinson's disease (PD) is a progressive neurological disorder associated with motor disabilities and cognitive dysfunction as well. Evidence indicates that PD occurs less frequently in women than men, confirming a role for steroid hormones in protection of dopaminergic nigrostriatal neurons. It is reported that soy genistein, an estrogen agonist phytoestrogen, display neuroprotective effects against neuronal death. In this study we evaluated the effect of genistein in animal models of Parkinsonism (P) and Parkinsonism + ovariectomized (OP)...
December 2016: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/28096359/%C3%AE-synuclein-binds-and-sequesters-pike-l-into-lewy-bodies-triggering-dopaminergic-cell-death-via-ampk-hyperactivation
#7
Seong Su Kang, Zhentao Zhang, Xia Liu, Fredric P Manfredsson, Li He, P Michael Iuvone, Xuebing Cao, Yi E Sun, Lingjing Jin, Keqiang Ye
The abnormal aggregation of fibrillar α-synuclein in Lewy bodies plays a critical role in the pathogenesis of Parkinson's disease. However, the molecular mechanisms regulating α-synuclein pathological effects are incompletely understood. Here we show that α-synuclein binds phosphoinositide-3 kinase enhancer L (PIKE-L) in a phosphorylation-dependent manner and sequesters it in Lewy bodies, leading to dopaminergic cell death via AMP-activated protein kinase (AMPK) hyperactivation. α-Synuclein interacts with PIKE-L, an AMPK inhibitory binding partner, and this action is increased by S129 phosphorylation through AMPK and is decreased by Y125 phosphorylation via Src family kinase Fyn...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28095923/nadph-oxidase-in-brain-injury-and-neurodegenerative-disorders
#8
REVIEW
Merry W Ma, Jing Wang, Quanguang Zhang, Ruimin Wang, Krishnan M Dhandapani, Ratna K Vadlamudi, Darrell W Brann
Oxidative stress is a common denominator in the pathology of neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and multiple sclerosis, as well as in ischemic and traumatic brain injury. The brain is highly vulnerable to oxidative damage due to its high metabolic demand. However, therapies attempting to scavenge free radicals have shown little success. By shifting the focus to inhibit the generation of damaging free radicals, recent studies have identified NADPH oxidase as a major contributor to disease pathology...
January 17, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28095073/preclinical-and-potential-applications-of-common-western-herbal-supplements-as-complementary-treatment-in-parkinson-s-disease
#9
Luke A Morgan, Oliver Grundmann
Parkinson's disease (PD) is a neurological disorder with a complex pathological etiology, which is not fully understood. Progression of PD may be the result of a buildup of iron in the substantia nigra, microglia-mediated neuroinflammation, dysfunctional mitochondria, or abnormal protein handling. Dopamine is the main neurotransmitter affected, but as the disease progresses, a decrease in all the brain's biogenic amines occurs. Current medication used in the treatment of PD aims to prevent the breakdown of dopamine or increase dopaminergic neurotransmission in the central nervous system...
January 17, 2017: Journal of Dietary Supplements
https://www.readbyqxmd.com/read/28093210/neuroprotection-by-paeoniflorin-in-the-mptp-mouse-model-of-parkinson-s-disease
#10
Meizhu Zheng, Chunming Liu, Yajun Fan, Pan Yan, Dongfang Shi, Yuchi Zhang
Paeoniflorin (PF) is a major bioactive ingredient in Radix Paeonia alba roots that has low toxicity and has been shown to have neuroprotective effects. Our in vitro experiments suggested that PF affords a significant neuroprotective effect against MPP(+)-induced damage and apoptosis in PC12 cells through Bcl-2/Bax/caspase-3 pathway. The objectives of the present study were to explore the potential neuroprotective effect of PF in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-treated mouse model of Parkinson's disease (PD)...
January 13, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28093036/combining-nanoscale-magnetic-nimodipine-liposomes-with-magnetic-resonance-image-for-parkinson-s-disease-targeting-therapy
#11
Bingshuo Ji, Meili Wang, Dawei Gao, Shanshan Xing, Lei Li, Lanxiang Liu, Min Zhao, Ximing Qi, Kun Dai
AIM: To enhance drug targeting and blood-brain barrier penetration for Parkinson's disease (PD), a novel nanoscale magnetic nimodipine (NMD) delivery system was designed and prepared. MATERIALS & METHODS: The PD rats were established and treated with free NMD or Fe3O4-modified NMD liposomes (Fe3O4-NMD-lips). Then, factional anisotropy values were measured by MRI to evaluate therapy efficacy. RESULTS: Fe3O4-NMD-lips showed the best neuroprotective effect, and the NMD concentration of lesions was 2...
January 17, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28090177/the-effects-of-crocin-on-6-ohda-induced-oxidative-nitrosative-damage-and-motor-behaviour-in-hemiparkinsonian-rats
#12
Maryam Hosseini, Ziba Rajaei, Hojjatallah Alaei, Mohamadhasan Tajadini
BACKGROUND: Crocin is considered to prevent oxidative stress-related diseases, such as ischemia and Alzheimer's. The aim of the present investigation was to evaluate the effects of crocin on motor behaviour and 6-OHDA-induced oxidative/nitrosative damage to the striatum in an experimental model of Parkinson's disease. METHODS: Left medial forebrain bundle was lesioned by microinjection of 6-OHDA (16μg in 0.2% ascorbate-saline). Crocin (30 and 60 mg/kg) was injected intraperitoneally three days before surgery until six weeks...
November 2016: Malaysian Journal of Medical Sciences: MJMS
https://www.readbyqxmd.com/read/28088492/pikuni-blackfeet-traditional-medicine-neuroprotective-activities-of-medicinal-plants-used-to-treat-parkinson-s-disease-related-symptoms
#13
Aurélie de Rus Jacquet, Mitali Arun Tambe, Sin Ying Ma, George P McCabe, Jay Hansford C Vest, Jean-Christophe Rochet
ETHNOPHARMACOLOGICAL RELEVANCE: Parkinson's disease (PD) is a multifactorial neurodegenerative disorder affecting 5% of the population over the age of 85 years. Current treatments primarily involve dopamine replacement therapy, which leads to temporary relief of motor symptoms but fails to slow the underlying neurodegeneration. Thus, there is a need for safe PD therapies with neuroprotective activity. In this study, we analyzed contemporary herbal medicinal practices used by members of the Pikuni-Blackfeet tribe from Western Montana to treat PD-related symptoms, in an effort to identify medicinal plants that are affordable to traditional communities and accessible to larger populations...
January 11, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28087304/sleep-and-neurodegeneration-a-critical-appraisal
#14
REVIEW
Jagan A Pillai, James B Leverenz
Sleep abnormalities are clearly recognized as distinct clinical symptom of concern in neurodegenerative disorders. Appropriate management of sleep related symptoms has a positive impact on the quality of life of patients with neurodegenerative disorders. This review provides an overview of mechanisms that are currently being considered that tie sleep with neurodegeneration. It appraises the literature regarding specific sleep changes among common neurodegenerative diseases with a focus on Alzheimer's disease and synucleinopathies (i...
January 10, 2017: Chest
https://www.readbyqxmd.com/read/28079000/application-of-monoterpenoids-and-their-derivatives-for-treatment-of-neurodegenerative-disorders
#15
Konstantin P Volcho, Sergey S Laev, Ghulam Md Ashraf, Gjumrakch Aliev, Nariman F Salakhutdinov
Neurodegenerative disorders (NDDs) like Alzheimer disease, Parkinson's disease and Huntington's disease are a heterogeneous group of disorders with the progressive and severe loss of neurons. There are no full proof cures for these diseases, and only medicines are available that can alleviate some of the symptoms. Developing effective treatments for the NDDs is a difficult but necessary task. Hence, the investigation of monoterpenoids which modulate targets applicable to many NDDs is highly relevant. Many monoterpenoids have demonstrated promising neuroprotective activity mediated by various systems...
11, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28078613/l-f001-a-multifunction-rock-inhibitor-prevents-6-ohda-induced-cell-death-through-activating-akt-gsk-3beta-and-nrf2-ho-1-signaling-pathway-in-pc12-cells-and-attenuates-mptp-induced-dopamine-neuron-toxicity-in-mice
#16
Liting Luo, Jingkao Chen, Dan Su, Meihui Chen, Bingling Luo, Rongbiao Pi, Lan Wang, Wei Shen, Rikang Wang
Amounting evidences demonstrated that Rho/Rho-associated kinase (ROCK) might be a novel target for the therapy of Parkinson's disease (PD). Recently, we synthesized L-F001 and revealed it was a potent ROCK inhibitor with multifunctional effects. Here we investigated the effects of L-F001 in PD models. We found that L-F001 potently attenuated 6-OHDA-induced cytotoxicity in PC12 cells and significantly decreased intracellular reactive oxygen species (ROS), prevented the 6-OHDA-induced decline of mitochondrial membrane potential and intracellular GSH levels...
January 11, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28067625/pituitary-adenylate-cyclase-activating-polypeptide-pacap-has-neuroprotective-function-in-dopamine-based-neurodegeneration-developed-in-two-parkinsonian-models
#17
G Maasz, Z Zrinyi, D Reglodi, D Petrovics, A Rivnyak, T Kiss, A Jungling, A Tamas, Z Pirger
It has been observed that pituitary-adenylate cyclase activating polypeptide (PACAP) rescued DAergic neurons from neurodegeneration and improved motor alterations induced by 6-hydroxy-dopamine (6-OHDA) in rat parkinsonian models. Recently we investigated the molecular background of the neuroprotective effect of PACAP in DA-based neurodegeneration using rotenone-induced snail and 6-OHDA-induced rat models of Parkinson's disease. The behavioural activity, monoamine (DA and serotonin), metabolic enzyme (S-COMT, MB-COMT and MAO-B) and PARK7/DJ-1 protein contents were measured before and after PACAP-treatment in both models...
December 22, 2016: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28064330/blockade-of-fast-a-type-and-tea-sensitive-potassium-channels-provide-an-antiparkinsonian-effect-in-a-6-ohda-animal-model
#18
Hashem Haghdoost-Yazdi, Hossein Piri, Reza Najafipour, Ayda Faraji, Negin Fraidouni, Tahereh Dargahi, Mahmud Alipour Heidari
OBJECTIVE: To evaluate the effect of K+ channels inhibitors in treatment of parkinson`s disease (PD). METHODS: This prospective comparative study was conducted in the Qazvin University of Medical Sciences, Iran, from April 2015 to January 2016. Male rats (n=37) received intraperitoneal doses of TEA (2 and 5 mg/kg) or 4-AP (0.5 and 1 mg/kg) twice-daily, before a stereotactic injection of 6-hydroxydopamine (6-OHDA) for the following 7 days. The 6-OHDA was injected into right medial forebrain bundle (MFB) of the rat brains...
January 2017: Neurosciences: the Official Journal of the Pan Arab Union of Neurological Sciences
https://www.readbyqxmd.com/read/28063055/isolation-of-microglia-and-immune-infiltrates-from-mouse-and-primate-central-nervous-system
#19
Thais F Galatro, Ilia D Vainchtein, Nieske Brouwer, Erik W G M Boddeke, Bart J L Eggen
Microglia are the innate immune cells of the central nervous system (CNS) and play an important role in the maintenance of tissue homeostasis, providing neural support and neuroprotection. Microglia constantly survey their environment and quickly respond to homeostatic perturbations. Microglia are increasingly implicated in neuropathological and neurodegenerative conditions, such as Alzheimer's disease, Parkinson's disease, and glioma progression. Here, we describe a detailed isolation protocol for microglia and immune infiltrates, optimized for large amounts of post mortem tissue from human and rhesus macaque, as well as smaller tissue amounts from mouse brain and spinal cord, that yield a highly purified microglia population (up to 98 % purity)...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28060896/isobavachalcone-attenuates-mptp-induced-parkinson-s-disease-in-mice-by-inhibition-of-microglial-activation-through-nf-%C3%AE%C2%BAb-pathway
#20
Haoran Jing, Shaoxia Wang, Min Wang, Wenliang Fu, Chao Zhang, Donggang Xu
Parkinson's disease (PD) is a complex multi-system and age-related neurodegenerative disorder. The intervention targeting neuroinflammation in PD patients is one effective strategy to slow down or inhibit disease progression. Microglia-mediated inflammatory response plays an important role in Parkinson's, Alzheimer's and other cerebral diseases. Isobavachalcone is a main component of Chinese herb medicine Psoralea corylifolia, which function includes immunoregulation, anti-oxidation and the regulation of β-amyloid (Aβ42) deposited in hippocampus in Alzheimer's patients...
2017: PloS One
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