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Parkinson's disease and neuroprotection

Alberto Ascherio, Michael A Schwarzschild
Since 2006, several longitudinal studies have assessed environmental or behavioural factors that seem to modify the risk of developing Parkinson's disease. Increased risk of Parkinson's disease has been associated with exposure to pesticides, consumption of dairy products, history of melanoma, and traumatic brain injury, whereas a reduced risk has been reported in association with smoking, caffeine consumption, higher serum urate concentrations, physical activity, and use of ibuprofen and other common medications...
November 2016: Lancet Neurology
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
Daniel Enterría-Morales, Ivette López-López, José López-Barneo, Xavier d'Anglemont de Tassigny
Gender difference in Parkinson's disease (PD) suggests that female sex steroids may promote dopaminergic neuron survival and protect them from degeneration. The glial cell line-derived neurotrophic factor (GDNF) is believed to be dopaminotrophic; thus it is considered as a potential therapeutic target in PD. Additionally, GDNF is endogenously synthetized in the caudate/putamen of humans and striatum in rodents. A neuroprotective role of estrogens on the nigrostriatal pathway via the stimulation of GDNF has been proposed...
2016: PloS One
Tongkai Chen, Chuwen Li, Ye Li, Yi Xiang, Simon Ming Yuen Lee, Ying Zheng
Schisantherin A (SA) is a promising anti-Parkinsonism Chinese herbal medicine but with poor water solubility and challenges to be delivered to the brain. We formulated SA as nanocrystals (SA-NC), aiming to improve its solubility, pharmacokinetic profile and thus provide a potential therapeutic agent for the treatment of Parkinson's disease (PD). The rod-shaped SA-NC had a particle size of ~160 nm with 33.3% drug loading, and the nanocrystals exhibited a fast dissolution rate in vitro. The intact drug nanocrystals could be internalized into Madin-Darby canine kidney (MDCK) cells, which were followed by rapid intracellular release, and most of the drug was transported to the basolateral side in its soluble form...
October 14, 2016: Molecular Pharmaceutics
Wei Zhang, Hong He, Hujie Song, Junjie Zhao, Tao Li, Leitao Wu, Xiaojun Zhang, Jianzong Chen
The degenerative loss through apoptosis of dopaminergic neurons in the substantia nigra pars compacta plays a primary role in the progression of Parkinson's disease (PD). Our in vitro experiments suggested that salidroside (Sal) could protect against 1-methyl-4-phenylpyridine-induced cell apoptosis in part by regulating the PI3K/Akt/GSK3β pathway. The current study aims to increase our understanding of the protective mechanisms of Sal in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropypridine- (MPTP-) induced PD mouse model...
2016: Parkinson's Disease
Kai-Cheng Hsu, Feng-Sheng Wang
Model-based optimization approaches are valuable in developing new drugs for human metabolic disorders. The core objective in most optimal drug designs is positive therapeutic effects. In this study, we considered the effects of therapeutic, adverse, and target variation simultaneously. A fuzzy optimization method was applied to formulate a multiobjective drug design problem for detecting enzyme targets in the presynaptic dopamine metabolic network to remedy two types of enzymopathies caused by deficiencies of vesicular monoamine transporter 2 (VMAT2) and tyrosine hydroxylase (TH)...
2016: PloS One
Suraj S Pradhan, Kirstie Salinas, Alexis C Garduno, Jenny U Johansson, Qian Wang, Amy Manning-Bog, Katrin I Andreasson
Inflammation is a ubiquitous factor accompanying normal aging and neurodegeneration, and recent studies indicate a major contribution of inducible cyclooxygenase (COX-2) and its downstream prostaglandin signaling pathways in modulating neuroinflammatory responses and neuronal function. We have previously shown that the prostaglandin PGE2 receptor EP4 suppresses innate immune responses in models of systemic inflammation. Here we investigated the role of the EP4 receptor in models of Parkinson's disease (PD)...
October 12, 2016: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
Fernanda F Peres, Raquel Levin, Mayra A Suiama, Mariana C Diana, Douglas A Gouvêa, Valéria Almeida, Camila M Santos, Lisandro Lungato, Antônio W Zuardi, Jaime E C Hallak, José A Crippa, D'Almeida Vânia, Regina H Silva, Vanessa C Abílio
Cannabidiol (CBD) is a non-psychotomimetic compound from Cannabis sativa that presents antipsychotic, anxiolytic, anti-inflammatory, and neuroprotective effects. In Parkinson's disease patients, CBD is able to attenuate the psychotic symptoms induced by L-DOPA and to improve quality of life. Repeated administration of reserpine in rodents induces motor impairments that are accompanied by cognitive deficits, and has been applied to model both tardive dyskinesia and Parkinson's disease. The present study investigated whether CBD administration would attenuate reserpine-induced motor and cognitive impairments in rats...
2016: Frontiers in Pharmacology
Hongxiang Sun, Xiuquan He, Cejia Liu, Lingyu Li, Ruoyu Zhou, Tianyun Jin, Su Yue, Da Feng, Jie Gong, Jiawei Sun, Jianbo Ji, Lan Xiang
Oleracein E (OE), a tetrahydroisoquinoline possessing potent anti-oxidant activity, was first isolated from a traditional Chinese medicine, Portulaca oleraea L., and is hypothesized to be a neuroprotectant. In the present study, we evaluated the effects of racemic OE on rotenone-induced toxicity in Parkinson's disease (PD) cell and animal models. Pre-treatment with OE (10 μM, 2 h) decreased LDH release and the apoptosis rate in rotenone (5 μM, 24 h)-treated SH-SY5Y human neuroblastoma cells. Further mechanistic study indicated that OE reduced reactive oxygen species (ROS) levels, inhibited ERK1/2 phosphorylation, reduced rotenone-induced up-regulation of the proapoptotic protein Bax, and prevented cytochrome C release and caspase-3 activation...
October 12, 2016: ACS Chemical Neuroscience
Jingjing He, Zheng Xiang, Xiaoqing Zhu, Zongyong Ai, Jingsong Shen, Tianzhuang Huang, Liegang Liu, Weizhi Ji, Tianqing Li
Parkinson's disease (PD) is one common neurodegenerative disease caused by a significant loss of midbrain dopaminergic neurons. Previous reports showed that 7, 8- dihydroxyflavone (7, 8-DHF) as a potent TrkB agonist can mimic BDNF and play neuroprotective roles for mouse dopaminergic neurons. Nonetheless, the safety and neuroprotective effects are unclear in monkey models of PD. Here, we find that 7, 8-DHF could be absorbed and metabolized into 7-hydroxy-8-methoxyflavone through oral administration in monkeys...
October 12, 2016: Scientific Reports
Se Hee Oh, Ha Na Kim, Hyun Jung Park, Jin Young Shin, Dong Yeol Kim, Phil Hyu Lee
: : Ample evidence has suggested that extracellular α-synuclein aggregates would play key roles in the pathogenesis and progression of Parkinsonian disorders (PDs). In the present study, we investigated whether mesenchymal stem cells (MSCs) and their derived soluble factors could exert neuroprotective effects via proteolysis of extracellular α-synuclein. When preformed α-synuclein aggregates were incubated with MSC-conditioned medium, α-synuclein aggregates were disassembled, and insoluble and oligomeric forms of α-synuclein were markedly decreased, thus leading to a significant increase in neuronal viability...
October 11, 2016: Stem Cells Translational Medicine
Omar S Mabrouk
Parkinson's disease (PD) is a progressive neurodegenerative disorder that compromises multiple neurochemical substrates including dopamine, norepinephrine, serotonin, acetylcholine, and glutamate systems. Loss of these transmitter systems initiates a cascade of neurological deficits beginning with motor function and ending with dementia. Current therapies primarily address the motor symptoms of the disease via dopamine replacement therapy. Exogenous dopamine replacement brings about additional challenges since after years of treatment it almost invariably gives rise to dyskinesia as a side effect...
October 8, 2016: Handbook of Experimental Pharmacology
Weidong Le, Junjiao Wu, Yu Tang
Microglia-mediated neuroinflammation is a hallmark of Parkinson's disease (PD). In the brains of patients with PD, microglia have both neurotoxic and neuroprotective effects, depending on their activation state. In this review, we focus on recent research demonstrating the neuroprotective role of microglia in PD. Accumulating evidence indicates that the protective mechanisms of microglia may result from their regulation of transrepression pathways via nuclear receptors, anti-inflammatory responses, neuron-microglia crosstalk, histone modification, and microRNA regulation...
2016: Frontiers in Molecular Neuroscience
Caimei Gu, Xianying Yang, Linfang Huang
Cistanches Herba (family Orobanchaceae), commonly known as "desert ginseng" or Rou Cong Rong, is a global genus and commonly used for its neuroprotective, immunomodulatory, anti-oxidative, kidney impotence, laxative, anti-inflammatory, hepatoprotective, anti-bacterial, anti-viral, and anti-tumor effects in traditional herbal formulations in North Africa, Arabic, and Asian countries. The major bioactive compound present in this plant is phenylethanoid glycosides. In recent years, there has been great important in scientific investigation of the neuropharmacological effects of the bioactive compounds...
2016: Frontiers in Pharmacology
L Giancardo, A Sánchez-Ferro, T Arroyo-Gallego, I Butterworth, C S Mendoza, P Montero, M Matarazzo, J A Obeso, M L Gray, R San José Estépar
Parkinson's disease (PD) is a slowly progressing neurodegenerative disease with early manifestation of motor signs. Objective measurements of motor signs are of vital importance for diagnosing, monitoring and developing disease modifying therapies, particularly for the early stages of the disease when putative neuroprotective treatments could stop neurodegeneration. Current medical practice has limited tools to routinely monitor PD motor signs with enough frequency and without undue burden for patients and the healthcare system...
October 5, 2016: Scientific Reports
Richard Gordon, Matthew L Neal, Jie Luo, Monica R Langley, Dilshan S Harischandra, Nikhil Panicker, Adhithiya Charli, Huajun Jin, Vellareddy Anantharam, Trent M Woodruff, Qun-Yong Zhou, Anumantha G Kanthasamy, Arthi Kanthasamy
Prokineticin-2 (PK2), a recently discovered secreted protein, regulates important physiological functions including olfactory biogenesis and circadian rhythms in the CNS. Interestingly, although PK2 expression is low in the nigral system, its receptors are constitutively expressed on nigrostriatal neurons. Herein, we demonstrate that PK2 expression is highly induced in nigral dopaminergic neurons during early stages of degeneration in multiple models of Parkinson's disease (PD), including PK2 reporter mice and MitoPark mice...
October 5, 2016: Nature Communications
Giuseppe Arena, Enza Maria Valente
The gene PINK1 [phosphatase and tensin homolog (PTEN)-induced putative kinase 1] encodes a serine/threonine kinase which was initially linked to the pathogenesis of a familial form of Parkinson's disease. Research on PINK1 has recently unravelled that its multiple functions extend well beyond neuroprotection, implicating this eclectic protein in a growing number of human pathologies, including cancer, diabetes, cardiopulmonary dysfunctions and inflammation. Extensive studies have identified PINK1 as a crucial player in the mitochondrial quality control pathway, required to label damaged mitochondria and promote their elimination through an autophagic process (mitophagy)...
October 4, 2016: Journal of Pathology
Alireza Sarkaki, Yaghoob Farbood, Mojtaba Dolatshahi, Seyed Mohammad Taqhi Mansouri, Ali Khodadadi
Antioxidants have protective effects against free radicals-induced neural damage in Parkinson's disease (PD). We examined the effects of ellagic acid (EA) on locomotion, pallidal local EEG, and its frequency bands' power and also cerebral antioxidant contents in a rat model of PD induced by 6-hydroxidopamine (6-OHDA). 6-OHDA (16 µg/2µ l) was injected into the right medial forebrain bundle (MFB) in MFB-lesioned rat's brain. Sham group received vehicle instead of 6-OHDA. PD-model was confirmed by rotational test using apomorphine injection...
August 2016: Acta Medica Iranica
Débora Lanznaster, Tharine Dal-Cim, Tetsadê C B Piermartiri, Carla I Tasca
Guanosine is a purine nucleoside with important functions in cell metabolism and a protective role in response to degenerative diseases or injury. The past decade has seen major advances in identifying the modulatory role of extracellular action of guanosine in the central nervous system (CNS). Evidence from rodent and cell models show a number of neurotrophic and neuroprotective effects of guanosine preventing deleterious consequences of seizures, spinal cord injury, pain, mood disorders and aging-related diseases, such as ischemia, Parkinson's and Alzheimer's diseases...
October 2016: Aging and Disease
Nicholas V Skladnev, Varshika Ganeshan, Ji Yeon Kim, Thomas Burton, John Mitrofanis, Jonathan Stone, Daniel M Johnstone
Dietary saffron has shown promise as a neuroprotective intervention in clinical trials of retinal degeneration and dementia and in animal models of multiple CNS disorders, including Parkinson's disease. This therapeutic potential makes it important to define the relationship between dose and protection and the mechanisms involved. To explore these two issues, mice were pre-conditioned by providing an aqueous extract of saffron (0.01% w/v) as their drinking water for two, five or ten days before administration of the parkinsonian neurotoxin MPTP (50mg/kg)...
October 1, 2016: Journal of Neurochemistry
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