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Parkinson's disease and neuroprotection

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https://www.readbyqxmd.com/read/28634464/anti-inflammatory-and-neuroprotective-effects-of-co-ultrapealut-in-a-mouse-model-of-vascular-dementia
#1
Rosalba Siracusa, Daniela Impellizzeri, Marika Cordaro, Rosalia Crupi, Emanuela Esposito, Stefania Petrosino, Salvatore Cuzzocrea
Vascular dementia (VaD), the second most common cause of cognitive impairment in the population, is a disease that results from reduction in regional cerebral blood flow and involves oxidative stress and inflammation. Co-ultramicronized PEALut (co-ultra PEALut) is a new compound with beneficial effects, which include anti-inflammatory and antioxidant properties. Recently, co-ultraPEALut has been shown to exhibit neuroprotective effects in models of Parkinson's disease, cerebral ischemia and Alzheimer's disease...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28633346/tetramethylpyrazine-reverses-intracerebroventricular-streptozotocin-induced-memory-deficits-by-inhibiting-gsk-3%C3%AE
#2
Fen Lu, Xu Li, Wei Li, Ke Wei, Yong Yao, Qianlin Zhang, Xinliang Liang, Jiewen Zhang
Brain dysfunction, especially cognitive impairment, is one of the main complications in Alzheimer's disease (AD), which threatens the health of 46.8 million people worldwide. At present, the pathogenesis of cognitive dysfunction is only partially understood, and effective therapies for memory loss in AD remain elusive. Tetramethylpyrazine (TMP) is one of the major bioactive compounds purified from Chuanxiong, a Chinese herb used for the treatment of neurovascular and cardiovascular diseases. The neuroprotective properties of TMP are evident in some neurodegenerative diseases, including Parkinson's disease...
June 15, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28631231/2-3-dideoxycytidine-protects-dopaminergic-neurons-in-a-mouse-model-of-parkinson-s-disease
#3
Jianyi Niu, Jing Xiong, Dan Hu, Fei Zeng, Shuke Nie, Shanping Mao, Tao Wang, Zhentao Zhang, Zhaohui Zhang
DNA polymerase-β (DNA pol-β) plays a crucial role in the pathogenesis of Parkinson's disease (PD). The aim of this study was to investigate the neuroprotective effects of a DNA polymerase-β inhibitor 2',3'-dideoxycytidine (DDC) in PD models. In the in vitro studies, primary cultured neurons were challenged with 1-methyl-4-phenylpyridinium ion (MPP(+)). The expression of DNA pol-β was assessed using western blot. The neuroprotective effect of DNA pol-β knockdown and DNA pol-β inhibitor DDC was determined using cell viability assay and caspase-3 activity assay...
June 19, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28629580/folding-underlies-bidirectional-role-of-gpr37-pael-r-in-parkinson-disease
#4
REVIEW
Lina Leinartaité, Per Svenningsson
Since conformational flexibility, which is required for the function of a protein, comes at the expense of structural stability, many proteins, including G-protein-coupled receptors (GPCRs), are under constant risk of misfolding and aggregation. In this regard GPR37 (also named PAEL-R and ETBR-LP-1) takes a prominent role, particularly in relation to Parkinson disease (PD). GPR37 is a substrate for parkin and accumulates abnormally in autosomal recessive juvenile parkinsonism, contributing to endoplasmic reticulum stress and death of dopaminergic neurons...
June 16, 2017: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/28627590/activation-of-sonic-hedgehog-signal-by-purmorphamine-in-a-mouse-model-of-parkinson-s-disease-protects-dopaminergic-neurons-and-attenuates-inflammatory-response-by-mediating-pi3k-akt-signaling-pathway
#5
Shuai Shao, Guang-Liang Wang, Cespuglio Raymond, Xue-Hua Deng, Xiao-Lan Zhu, Di Wang, Le-Peng Hong
In Parkinson's disease (PD), microglial activation-mediated neuroinflammation is associated with dopaminergic neurons degeneration in the substantia nigra pars compacta. Previous studies that have investigated this neurodegenerative disease have reported that the Sonic hedgehog (SHH) signaling pathway, through inhibiting the inflammatory processes, exerts a beneficial neuroprotective effect. However, the mechanisms underlying the anti‑inflammatory and neuroprotective effects of this signaling pathway remain poorly understood...
June 9, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28627426/neurodegenerative-signaling-factors-and-mechanisms-in-parkinson-s-pathology
#6
REVIEW
Poonam Goswami, Neeraj Joshi, Sarika Singh
Parkinson's disease (PD) is a chronic and progressive degenerative disorder of central nervous system which is mainly characterized by selective loss of dopaminergic neurons in the nigrostrial pathway. Clinical symptoms of this devastating disease comprise motor impairments such as resting tremor, bradykinesia, postural instability and rigidity. Current medications only provide symptomatic relief but fail to halt the dopaminergic neuronal death. While the etiology of dopaminergic neuronal death is not fully understood, combination of various molecular mechanisms seems to play a critical role...
June 13, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28623717/baicalein-exerts-anti-neuroinflammatory-effects-to-protect-against-rotenone-induced-brain-injury-in-rats
#7
Xue Zhang, Yulin Yang, Lida Du, Wen Zhang, Guanhua Du
Baicalein, a major bioactive flavone constituent isolated from Scutellaria baicalensis Georgi, has been shown to be neuroprotective in several Parkinson's disease (PD) animal models. Since neuroinflammation has been known to play a critical role in the pathogenesis of PD, potential explanation for the neuroprotective action of anti-PD compounds involves among others reduced inflammation. Our study investigated that one of the mechanisms of protection afforded by baicalein in rotenone-induced parkinsonian rats was associated with anti-inflammatory action and explored its underlying mechanism in vivo and in vitro...
June 14, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28623709/the-mechanism-of-neuroprotective-action-of-natural-compounds
#8
REVIEW
Agnieszka Wąsik, Lucyna Antkiewicz-Michaluk
Disturbance of cerebral redox homeostasis is the primary cause of human neurodegenerative disorders, such as Parkinson's disease or Alzheimer's disease. Well known experimental research demonstrates that oxidative stress is a main cause of cell death. A high concentration of reactive oxygen and nitrogen species leads to damage of a lot of proteins, lipids and also DNA. Synthetic compounds used for the treatment in the neurodegenerative diseases failed to meet the hopes they had raised and often exhibit a number of side effects...
April 30, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28622913/targeting-urate-to-reduce-oxidative-stress-in-parkinson-disease
#9
REVIEW
Grace F Crotty, Alberto Ascherio, Michael A Schwarzschild
Oxidative stress has been implicated as a core contributor to the initiation and progression of multiple neurological diseases. Genetic and environmental factors can produce oxidative stress through mitochondrial dysfunction leading to the degeneration of dopaminergic and other neurons underlying Parkinson disease (PD). Although clinical trials of antioxidants have thus far failed to demonstrate slowed progression of PD, oxidative stress remains a compelling target. Rather than prompting abandonment of antioxidant strategies, these failures have raised the bar for justifying drug and dosing selections and for improving study designs to test for disease modification by antioxidants...
June 13, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28622912/clinical-approaches-to-the-development-of-a-neuroprotective-therapy-for-pd
#10
REVIEW
C W Olanow, K Kieburtz, R Katz
The development of a neuroprotective or disease-modifying therapy is the major unmet need in the management of Parkinson's Disease (PD) and the goal of much clinical and scientific research. However, despite enormous efforts and expense, no disease-modifying therapy for PD has been approved to date. Historically attempts to define such a therapy have been limited by confounding symptomatic/pharmacologic effects of the study intervention and the lack of a clear and well-defined regulatory and clinical development pathway that leads to a disease-modifying indication...
June 13, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28622392/therapeutic-efficacy-of-aav8-mediated-intrastriatal-delivery-of-human-cerebral-dopamine-neurotrophic-factor-in-6-ohda-induced-parkinsonian-rat-models-with-different-disease-progression
#11
Lizheng Wang, Zixuan Wang, Rui Zhu, Jinpeng Bi, Xinyao Feng, Wenmo Liu, Jiaxin Wu, Haihong Zhang, Hui Wu, Wei Kong, Bin Yu, Xianghui Yu
Parkinson's disease (PD) is a progressive and age-associated neurodegenerative disorder. Patients at different stages of the disease course have distinguished features, mainly in the number of dopaminergic neurons. Cerebral dopamine neurotrophic factor (CDNF) is a recently discovered neurotrophic factor, being deemed as a hopeful candidate for PD treatment. Here, we evaluated the efficacy of CDNF in protecting dopaminergic function using the 6-OHDA-induced PD rat model suffering from different levels of neuronal loss and the recombinant adeno-associated virus 8 (AAV8) as a carrier for the CDNF gene...
2017: PloS One
https://www.readbyqxmd.com/read/28619286/neuroprotective-potential-of-aloe-arborescens-against-copper-induced-neurobehavioral-features-of-parkinson-s-disease-in-rat
#12
Abdellatif Abbaoui, Omar El Hiba, Halima Gamrani
Copper (Cu) is an important trace element for the organism survival, which ensures the normal functioning of different biosystems. However, excessive levels of this heavy metal are responsible for profound physiological alterations including the central nervous system. Numerous findings sustain the involvement of heavy metals, as an environmental risk factor such as copper (Cu), in the neuropathology of Parkinson's disease (PD) which is a chronic neurodegenerative disorder that principally affects the motor system...
June 12, 2017: Acta Histochemica
https://www.readbyqxmd.com/read/28618343/design-synthesis-immunocytochemistry-evaluation-and-molecular-docking-investigation-of-several-4-aminopyridine-derivatives-as-potential-neuroprotective-agents-for-treating-parkinson-s-disease
#13
Shulin Li, Daiyan Wei, Zhuo Mao, Ligong Chen, Xilong Yan, Yang Li, Shengjie Dong, Donghua Wang
Neuroprotection refers to the relative preservation of neuronal structure and function. Neuroprotective agents refer to substances that are capable of preserving brain function and structure. Currently, there are no neuroprotective agents available that can effectively relieve the progression of Parkinson's disease. In this work, five novel 4-aminopyridine derivatives, including three amides and two ureas, were designed, synthesized, and evaluated using the rat PC12 mice pheochromocytoma cell line as an in vitro model...
May 31, 2017: Bioorganic Chemistry
https://www.readbyqxmd.com/read/28615996/international-society-of-sports-nutrition-position-stand-safety-and-efficacy-of-creatine-supplementation-in-exercise-sport-and-medicine
#14
REVIEW
Richard B Kreider, Douglas S Kalman, Jose Antonio, Tim N Ziegenfuss, Robert Wildman, Rick Collins, Darren G Candow, Susan M Kleiner, Anthony L Almada, Hector L Lopez
Creatine is one of the most popular nutritional ergogenic aids for athletes. Studies have consistently shown that creatine supplementation increases intramuscular creatine concentrations which may help explain the observed improvements in high intensity exercise performance leading to greater training adaptations. In addition to athletic and exercise improvement, research has shown that creatine supplementation may enhance post-exercise recovery, injury prevention, thermoregulation, rehabilitation, and concussion and/or spinal cord neuroprotection...
2017: Journal of the International Society of Sports Nutrition
https://www.readbyqxmd.com/read/28615451/molecular-mechanisms-of-signaling-via-the-docosanoid-neuroprotectin-d1-for-cellular-homeostasis-and-neuroprotection
#15
Aram Asatryan, Nicolas G Bazan
Docosahexaenoic acid (DHA), an omega-3 essential fatty acid family member that is enriched in the nervous system, generates bioactive docosanoids that can counteract disruptions of cellular homeostasis. Docosanoids include neuroprotectin D1 (NPD1), which is decreased in the CA1 hippocampal area of patients with early-stage Alzheimers disease (AD). We summarize here how NPD1 elicits neuroprotection by up-regulating c-REL, a nuclear factor (NF)-kappaB subtype that, in turn, enhances expression of BIRC3 (baculoviral IAP repeat-containing protein 3, or cIAP2) in retinal cells...
June 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28611572/4r-cembranoid-improves-outcomes-after-6-hydroxydopamine-challenge-in-both-in-vitro-and-in-vivo-models-of-parkinson-s-disease
#16
Jing Hu, P A Ferchmin, Ann M Hemmerle, Kim B Seroogy, Vesna A Eterovic, Jiukuan Hao
(1S, 2E, 4R, 6R,-7E, 11E)-2, 7, 11-cembratriene-4, 6-diol (4R) is one of the cembranoids found in tobacco leaves. Previous studies have found that 4R protected acute rat hippocampal slices against neurotoxicity induced by N-methyl-D-aspartate (NMDA) and against the toxic organophosphorus compounds paraoxon and diisopropylfluorophosphate (DFP). Furthermore, in vivo, 4R reduced the infarct size in a rodent ischemic stroke model and neurodegeneration caused by DFP. The present study expanded our previous study by focusing on the effect of 4R in Parkinson's disease (PD) and elucidating its underlying mechanisms using 6-hydroxydopamine (6-OHDA)-induced injury models...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28611284/activation-of-the-atf2-creb-pgc-1%C3%AE-pathway-by-metformin-leads-to-dopaminergic-neuroprotection
#17
Hojin Kang, Rin Khang, Sangwoo Ham, Ga Ram Jeong, Hyojung Kim, Minkyung Jo, Byoung Dae Lee, Yun Il Lee, Areum Jo, Chi Hu Park, Hyein Kim, Jeongkon Seo, Sun Ha Paek, Yun-Song Lee, Jeong-Yun Choi, Yunjong Lee, Joo-Ho Shin
Progressive dopaminergic neurodegeneration is responsible for the canonical motor deficits in Parkinson's disease (PD). The widely prescribed anti-diabetic medicine metformin is effective in preventing neurodegeneration in animal models; however, despite the significant potential of metformin for treating PD, the therapeutic effects and molecular mechanisms underlying dopaminergic neuroprotection by metformin are largely unknown.In this study, we found that metformin induced substantial proteomic changes, especially in metabolic and mitochondrial pathways in the substantia nigra (SN)...
May 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28610743/valproate-and-sodium-butyrate-attenuate-manganese-decreased-locomotor-activity-and-astrocytic-glutamate-transporters-expression-in-mice
#18
James Johnson, Edward Alain B Pajarillo, Equar Taka, Romonia Reams, Deok-Soo Son, Michael Aschner, Eunsook Lee
Manganese (Mn) is an essential trace element, but chronic overexposure to this metal, either environmentally or occupationally may cause manganism, a disease analogous to Parkinson's disease. Inhibitors of histone deacetylases, such as valproic acid (VPA) and sodium butyrate (NaB) exert neuroprotective effects in various animal models of neurological disorders. Thus, the present study investigated whether VPA or NaB prevent Mn-induced neurotoxicity by assessing locomotor activities and expression of astrocytic glutamate transporters, glutamate transporter 1 (GLT-1) and glutamate aspartate transporter (GLAST), in C57BL/6 mice...
June 10, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/28608752/ferulic-acid-and-its-water-soluble-derivatives-inhibit-nitric-oxide-production-and-inducible-nitric-oxide-synthase-expression-in-rat-primary-astrocytes
#19
Masaki Kikugawa, Tomoaki Ida, Hideshi Ihara, Tatsuji Sakamoto
We recently reported that two water-soluble derivatives of ferulic acid (1-feruloyl glycerol, 1-feruloyl diglycerol) previously developed by our group exhibited protective effects against amyloid-β-induced neurodegeneration in vitro and in vivo. In the current study, we aimed to further understand this process by examining the derivatives' ability to suppress abnormal activation of astrocytes, the key event of neurodegeneration. We investigated the effects of ferulic acid (FA) derivatives on nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression in rat primary astrocytes...
June 13, 2017: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/28608697/perspectives-of-cannabinoid-type-2-receptor-cb2r-ligands-in-neurodegenerative-disorders-structure-affinity-relationship-safir-and-structure-activity-relationship-sar-studies
#20
Francesco Spinelli, Elena Capparelli, Carmen Abate, Nicola A Colabufo, Marialessandra Contino
Up-regulation of CB2R on activated microglial cells, the first step in neurodegeneration, has been widely demonstrated, and this finding makes the receptor a promising target in the early diagnosis and treatment of several neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and multiple sclerosis (MS). The development of CB2R PET ligands could help demonstrate the neurodegenerative pathogenesis, thus providing useful tools for characterizing the role of neuroinflammation in the progression of these disorders...
June 13, 2017: Journal of Medicinal Chemistry
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