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https://www.readbyqxmd.com/read/28214632/synthesis-of-new-heterocyclic-compounds-based-on-pyrazolopyridine-scaffold-and-evaluation-of-their-neuroprotective-potential-in-mpp-induced-neurodegeneration
#1
Jabrane Jouha, Mohammed Loubidi, Jamila Bouali, Salha Hamri, Abderrafia Hafid, Franck Suzenet, Gérald Guillaumet, Taner Dagcı, Mostafa Khouili, Fadime Aydın, Luciano Saso, Güliz Armagan
Neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, and Huntington's disease affect millions of people in the world. Thus several new approaches to treat brain disorders are under development. The aim of the present study is to synthesize potential neuroprotective heterocyclic compounds based on pyrazolopyridine derivatives and then to evaluate their effects in MPP(+)-induced neurodegeneration in human neuroblastoma cell line (SH-SY5Y cells). The effects of the compounds on cell viability were measured by MTT assay and the changes in apoptosis-related proteins including bax, Bcl-2, Bcl-xl and caspase-3 were investigated by western blot technique...
February 11, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28214539/lumbee-traditional-medicine-neuroprotective-activities-of-medicinal-plants-used-to-treat-parkinson-s-disease-related-symptoms
#2
Aurélie de Rus Jacquet, Michael Timmers, Sin Ying Ma, Andrew Thieme, George P McCabe, Jay Hansford C Vest, Mary Ann Lila, Jean-Christophe Rochet
ETHNOPHARMACOLOGICAL RELEVANCE: Parkinson's disease (PD) is a neurodegenerative disorder characterized by a loss of dopaminergic neurons in the substantia nigra pars compacta and the presence in surviving neurons of Lewy body inclusions enriched with aggregated forms of the presynaptic protein α-synuclein (aSyn). Although current therapies provide temporary symptomatic relief, they do not slow the underlying neurodegeneration in the midbrain. In this study, we analyzed contemporary herbal medicinal practices used by members of the Lumbee tribe to treat PD-related symptoms, in an effort to identify safe and effective herbal medicines to treat PD...
February 15, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28214378/calcium-signaling-through-l-type-calcium-channels-role-in-pathophysiology-of-spinal-nociceptive-transmission
#3
REVIEW
Olivier Roca-Lapirot, Houda Radwani, Franck Aby, Frédéric Nagy, Marc Landry Pascal Fossat
L-type voltage-gated calcium channels (VGCCs) are ubiquitous channels in the central nervous system. L-type calcium channels (LTCs) are mostly post-synaptic channels regulating neuronal firing and gene expression. They play a role in important physio-pathological processes such as learning and memory, Parkinson's disease, autism and, as recognized more recently, in the pathophysiology of pain processes. Classically, the fundamental role of these channels in cardiovascular functions has limited the use of classical molecules to treat LTC-dependent disorders...
February 18, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28214265/association-between-dopaminergic-dysfunction-and-anxiety-in-de-novo-parkinson-s-disease
#4
Marina Picillo, Gabriella Santangelo, Roberto Erro, Autilia Cozzolino, Marianna Amboni, Carmine Vitale, Paolo Barone, Maria Teresa Pellecchia
OBJECTIVES: To explore the relationships between nigrostriatal dysfunction and neuropsychiatric symptoms (including anxiety, depression and apathy) in a large cohort of newly diagnosed, drug-naïve Parkinson disease (PD) patients compared to a cohort of healthy controls (HC). METHODS: This is a cross-sectional analysis of the Parkinson's Progression Markers Initiative (PPMI) cohort at baseline, including 405 PD patients and 187 HC. Nigrostriatal degeneration was evaluated by means of SPECT DAT scan...
February 9, 2017: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/28214264/identification-of-candidate-cerebrospinal-fluid-biomarkers-in-parkinsonism-using-quantitative-proteomics
#5
N K Magdalinou, A J Noyce, R Pinto, E Lindstrom, J Holmén-Larsson, M Holtta, K Blennow, H R Morris, T Skillbäck, T T Warner, A J Lees, I Pike, M Ward, H Zetterberg, J Gobom
INTRODUCTION: Neurodegenerative parkinsonian syndromes have significant clinical and pathological overlap, making early diagnosis difficult. Cerebrospinal fluid (CSF) biomarkers may aid the differentiation of these disorders, but other than α-synuclein and neurofilament light chain protein, which have limited diagnostic power, specific protein biomarkers remain elusive. OBJECTIVES: To study disease mechanisms and identify possible CSF diagnostic biomarkers through discovery proteomics, which discriminate parkinsonian syndromes from healthy controls...
January 31, 2017: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/28214109/a-novel-mutation-in-trem2-gene-causing-nasu-hakola-disease-and-review-of-the-literature
#6
Efthimios Dardiotis, Vasileios Siokas, Eva Pantazi, Maria Dardioti, Dimitrios Rikos, Georgia Xiromerisiou, Aikaterini Markou, Dimitra Papadimitriou, Matthaios Speletas, Georgios M Hadjigeorgiou
Nasu-hakola disease (NHD) is a rare disease characterized by bone cysts and fractures, frontal lobe syndrome, and progressive presenile dementia. NHD may be the prototype of primary microglial disorders of the CNS or, as they have been coined, "microgliopathies". Mutations in TREM2 and TYROBP genes are known to cause NHD. Interestingly, recent evidence-associated rare genetic variants of TREM2 gene with increased risk of Alzheimer's disease, frontotemporal dementia, amyotrophic lateral sclerosis, and Parkinson's disease...
January 20, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28213892/opportunities-for-repurposing-of-poly-adp-ribose-polymerase-parp-inhibitors-for-the-therapy-of-non-oncological-diseases
#7
REVIEW
Nathan A Berger, Valerie C Besson, A Hamid Boulares, Alexander Bürkle, Alberto Chiarugi, Robert S Clark, Nicola J Curtin, Salvatore Cuzzocrea, Ted M Dawson, Valina L Dawson, György Haskó, Lucas Liaudet, Flavio Moroni, Pál Pacher, Peter Radermacher, Andrew L Salzman, Solomon H Snyder, Francisco Garcia Soriano, Robert P Strosznajder, Balázs Sümegi, Raymond A Swanson, Csaba Szabo
The recent clinical availability of the PARP inhibitor Lynparza (olaparib) opens the door for potential therapeutic repurposing for non-oncological indications. Considering (a) the preclinical efficacy data with PARP inhibitors in non-oncological diseases and (b) the risk-benefit ratio of treating patients with a compound that inhibits an enzyme that has physiological roles in the regulation of DNA repair, indications where (a) the severity of the disease is high, (b) the available therapeutic options are limited, and (c) the duration of PARP inhibitor administration could be short, provide first-line options for therapeutic repurposing...
February 18, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28213762/association-between-cognitive-impairment-and-urinary-dysfunction-in-parkinson-s-disease
#8
Zuzanna Tkaczynska, Andrea Pilotto, Sara Becker, Susanne Gräber-Sultan, Daniela Berg, Inga Liepelt-Scarfone
Urinary dysfunction (UD) is a common non-motor feature of Parkinson's disease (PD), and might be secondary to neurodegeneration involving cortical and subcortical brain areas. The possible link between UD and cognitive deficits has never been examined in frontal cortex impairment, and is still not completely understood in PD. In the present study, 94 PD patients underwent a comprehensive motor, cognitive and non-motor assessment. It was shown that 55.3% of patients reported UD, of which 17% needed specific urological treatment...
February 17, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28213756/-diagnostics-of-clinical-and-prodromal-idiopathic-parkinson-s-disease-new-criteria
#9
H Zach, U Walter, I Liepelt-Scarfone, W Maetzler
BACKGROUND: Recently, the Movement Disorder Society (MDS) published an adaptation of the previous United Kingdom Brain Bank Society (UKBBS) criteria for the diagnosis of idiopathic Parkinson's disease (iPD). OBJECTIVES: This article presents the changes in the current clinical diagnostic criteria for IPD. Furthermore, the new MDS criteria for prodromal iPD are discussed. RESULTS: The recently introduced MDS criteria for the clinical diagnosis of iPD include useful novel features (e...
February 17, 2017: Der Nervenarzt
https://www.readbyqxmd.com/read/28213435/genetics-of-synucleinopathies
#10
Robert L Nussbaum
Parkinson's disease (PD), diffuse Lewy body disease (DLBD), and multiple system atrophy (MSA) constitute the three major neurodegenerative disorders referred to as synucleinopathies because both genetic and pathological results implicate the α-synuclein protein in their pathogenesis. PD and DLBD are recognized as closely related diseases with substantial clinical and pathological overlap. MSA, on the other hand, has a distinctive clinical presentation and neuropathological profile. In this review, we will summarize the evidence linking α-synuclein to these three disorders...
February 17, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28213158/pink1-parkin-mitophagy-and-neurodegeneration-what-do-we-really-know-in-vivo
#11
REVIEW
Alexander J Whitworth, Leo J Pallanck
Mitochondria are essential organelles that provide cellular energy and buffer cytoplasmic calcium. At the same time they produce damaging reactive oxygen species and sequester pro-apoptotic factors. Hence, eukaryotes have evolved exquisite homeostatic processes that maintain mitochondrial integrity, or ultimately remove damaged organelles. This subject has garnered intense interest recently following the discovery that two Parkinson's disease genes, PINK1 and parkin, regulate mitochondrial degradation (mitophagy)...
February 14, 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/28213071/pla2g6-accumulates-in-lewy-bodies-in-park14-and-idiopathic-parkinson-s-disease
#12
Yasuo Miki, Kunikazu Tanji, Fumiaki Mori, Akiyoshi Kakita, Hitoshi Takahashi, Koichi Wakabayashi
The histopathological hallmark of Parkinson's disease (PD) and dementia with Lewy bodies (DLB) is the occurrence of insoluble fibrillary aggregates known as Lewy bodies, in which phosphorylated α-synuclein (α-syn) is a major component. To date, familial PD-linked gene products, including α-syn, parkin, PINK-1, DJ-1 and LRRK2, are known to be involved in Lewy body formation. Phospholipase A2, group VI (PLA2G6) is the causative gene for PARK14-linked parkinsonism (PARK14), a familial form of juvenile-onset dystonia parkinsonism...
February 14, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28213070/selective-a2a-receptors-blockade-reduces-degeneration-of-substantia-nigra-dopamine-neurons-in-a-rotenone-induced-rat-model-of-parkinson-s-disease-a-histological-study
#13
Ahmed M Fathalla, Amira M Soliman, Ahmed A Moustafa
Parkinson's disease (PD) is characterized by a loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Adenosine is a neuromodulator that inhibit the release of dopamine via a disinhibitory mechanism. In this study, we investigated the neuroprotective effect of 8-cyclopentyl-1,3-dipropylxanthine and ZM241385 (respectively, A1 and A2A receptors antagonists), on nigrostriatal dopamine neurons degradation reduction in a rotenone-induced PD model using histopathological and immunohistochemical methods...
February 14, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28212928/nonmotor-symptoms-in-de-novo-parkinson-disease-comparing-to-normal-aging
#14
Petra Bago Rožanković, Marjan Rožanković, Lovorka Vučak Novosel, Maristela Stojić
OBJECTIVE: Nonmotor symptoms (NMSs) are common in Parkinson disease (PD), affecting patient's quality of life. The prevalence and domains of NMSs in untreated de novo PD remains unclear, especially comparing to normal aging. The objective was to determine NMSs in untreated de novo PD patients. PATIENTS AND METHODS: We performed a cross-sectional study to evaluate the frequency and severity of NMSs in untreated de novo PD patients (n=71) and age-matched normal controls (n=60) using the Non-Motor Symptoms Scale (NMSS)...
February 11, 2017: Clinical Neurology and Neurosurgery
https://www.readbyqxmd.com/read/28212832/motor-dysfunction-and-alterations-in-glutathione-concentration-cholinesterase-activity-and-bdnf-expression-in-substantia-nigra-pars-compacta-in-rats-with-pedunculopontine-lesion
#15
Lisette Blanco-Lezcano, Javier Jimenez-Martin, Mei-Li Díaz-Hung, Esteban Alberti-Amador, Maylin Wong-Guerra, Ma Elena González-Fraguela, Bárbara Estupiñán-Díaz, Teresa Serrano-Sánchez, Liliana Francis-Turner, Susana Delgado-Ocaña, Yanier Núñez-Figueredo, Yamilé Vega-Hurtado, Isabel Fernández-Jiménez
Pedunculopontine nucleus (PPN) has been considered a critically important region in the regulation of some of the physiological functions that fail during the progression of Parkinson's disease (PD). In this paper, the effects of unilateral neurotoxic lesion of the PPN [through the injection of N-methyl-D-aspartate (NMDA) solution (concentration: 0.1 M; volume: 0.5 µL)] in motor execution and gait disorders and the changes in cellular and molecular indicators in rat nigral tissue were evaluated. The motor execution was assessed using the beam test (BT) and the gait disorders by footprint test...
February 14, 2017: Neuroscience
https://www.readbyqxmd.com/read/28212723/redox-dynamics-of-manganese-as-a-mitochondrial-life-death-switch
#16
REVIEW
Matthew Ryan Smith, Jolyn Fernandes, Young-Mi Go, Dean P Jones
Sten Orrenius, M.D., Ph.D., pioneered many areas of cellular and molecular toxicology and made seminal contributions to our knowledge of oxidative stress and glutathione (GSH) metabolism, organellar functions and Ca(+2)-dependent mechanisms of cell death, and mechanisms of apoptosis. On the occasion of his 80(th) birthday, we summarize current knowledge on redox biology of manganese (Mn) and its role in mechanisms of cell death. Mn is found in all organisms and has critical roles in cell survival and death mechanisms by regulating Mn-containing enzymes such as manganese superoxide dismutase (SOD2) or affecting expression and activity of caspases...
January 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28212694/suvorexant-induced-dream-enactment-behavior-in-parkinson-disease-a-case-report
#17
Hiromitsu Tabata, Akira Kuriyama, Fusae Yamao, Hiroshi Kitaguchi, Katsuro Shindo
Suvorexant is a new insomnia drug, and it is generally safe and well tolerated. Here, we report a rare but potentially important adverse effect of suvorexant in a patient with Parkinson disease.
February 15, 2017: Journal of Clinical Sleep Medicine: JCSM: Official Publication of the American Academy of Sleep Medicine
https://www.readbyqxmd.com/read/28212433/elevated-gm3-plasma-concentration-in-idiopathic-parkinson-s-disease-a-lipidomic-analysis
#18
Robin B Chan, Adler J Perotte, Bowen Zhou, Christopher Liong, Evan J Shorr, Karen S Marder, Un J Kang, Cheryl H Waters, Oren A Levy, Yimeng Xu, Hong Bin Shim, Itsik Pe'er, Gilbert Di Paolo, Roy N Alcalay
Parkinson's disease (PD) is a common neurodegenerative disease whose pathological hallmark is the accumulation of intracellular α-synuclein aggregates in Lewy bodies. Lipid metabolism dysregulation may play a significant role in PD pathogenesis; however, large plasma lipidomic studies in PD are lacking. In the current study, we analyzed the lipidomic profile of plasma obtained from 150 idiopathic PD patients and 100 controls, taken from the 'Spot' study at Columbia University Medical Center in New York. Our mass spectrometry based analytical panel consisted of 520 lipid species from 39 lipid subclasses including all major classes of glycerophospholipids, sphingolipids, glycerolipids and sterols...
2017: PloS One
https://www.readbyqxmd.com/read/28212408/prevalence-and-associated-comorbidities-of-restless-legs-syndrome-rls-data-from-a-large-population-based-door-to-door-survey-on-19176-adults-in-tehran-iran
#19
Seyed-Mohammad Fereshtehnejad, Arash Rahmani, Mahdiyeh Shafieesabet, Mahshid Soori, Ahmad Delbari, Mohammad Reza Motamed, Johan Lökk
BACKGROUND: Discrepancies have been reported in the prevalence rate of restless legs syndrome (RLS) among different ethnic groups and geographic populations. Furthermore, there are disagreements on determinant factors and associated comorbidities of RLS. We aimed to estimate prevalence of RLS and investigate its associated comorbid conditions and risk factors in a large population-based door-to-door survey. METHODS: Following a multistage random sampling from the households lived in 22 urban districts of Tehran, Iran, 19176 participants with ≥30 years of age were recruited...
2017: PloS One
https://www.readbyqxmd.com/read/28212331/analysis-of-epidermal-growth-factor-receptor-related-gene-expression-changes-in-a-cellular-and-animal-model-of-parkinson-s-disease
#20
In-Su Kim, Sushruta Koppula, Shin-Young Park, Dong-Kug Choi
We employed transcriptome analysis of epidermal growth factor receptor related gene expression changes in cellular and animal models of Parkinson's disease (PD). We used a well-known Parkinsonian toxin 1-methyl-4-phenylpyridine (MPP⁺) to induce neuronal apoptosis in the human neuroblastoma SH-SY5Y cell line. The MPP⁺-treatment of SH-SY5Y cells was capable of inducing neuro-apoptosis, but it remains unclear what kinds of transcriptional genes are affected by MPP⁺ toxicity. Therefore the pathways that were significantly perturbed in MPP⁺ treated human neuroblastoma SH-SY5Y cells were identified based on genome-wide gene expression data at two time points (24 and 48 h)...
February 16, 2017: International Journal of Molecular Sciences
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