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Cinnamon and its Metabolite Protect the Nigrostriatum in a Mouse Model of Parkinson ’s Disease Via Astrocytic GDNF
This study underlines the importance of sodium benzoate (NaB), a metabolite of commonly-used spice cinnamon, a food-additive and an FDA-approved drug against hyperammonemia, in stimulating GDNF in primary mouse and human astrocytes. Presence of cAMP response element (CRE) in theGdnf gene promoter, recruitment of CREB to theGdnf promoter by NaB and abrogation of NaB-mediated GDNF expression by siRNA knockdown of CREB suggest that NaB induces the transcription ofGdnf via CREB. Finally, oral administration of NaB and cinnamon itself increased the level of GDNF in vivo in the substantia nigra pars compacta (SNpc) of normal as ...
Source: Journal of NeuroImmune Pharmacology - May 21, 2019 Category: Drugs & Pharmacology Source Type: research

Connecting Metainflammation and Neuroinflammation Through the PTN-MK-RPTP β/ζ Axis: Relevance in Therapeutic Development
Conclusion The expression of the components of the PTN-MK-RPTPβ/ζ axis in immune cells and in inflammatory diseases suggests important roles for this axis in inflammation. Pleiotrophin has been recently identified as a limiting factor of metainflammation, a chronic pathological state that contributes to neuroinflammation and neurodegeneration. Pleiotrophin also seems to potentiate acute neuroinflammation independently of the inflammatory stimulus while MK seems to play different -even opposite- roles in acute neuroinflammation depending on the stimulus. Which are the functions of MK and PTN in chronic neuroi...
Source: Frontiers in Pharmacology - April 11, 2019 Category: Drugs & Pharmacology Source Type: research

Low-Dose Aspirin Upregulates Tyrosine Hydroxylase and Increases Dopamine Production in Dopaminergic Neurons: Implications for Parkinson ’s Disease
This study underlines the importance of aspirin in stimulating the expression of TH and increasing the level of DA in dopaminergic neurons. At low doses, aspirin increased the expression of TH and the production of DA in mouse MN9D dopaminergic neuronal cells. Accordingly, oral administration of aspirin increased the expression of TH in the nigra and upregulated the level of DA in striatum of normal C57/BL6 mice and aged A53T α-syn transgenic mice. Oral aspirin also improved locomotor activities of normal mice and A53T transgenic mice. While investigating mechanisms, we found the presence of cAMP response element (CRE) in...
Source: Journal of NeuroImmune Pharmacology - September 5, 2018 Category: Drugs & Pharmacology Source Type: research

Wnt/ β-catenin signaling plays an essential role in α7 nicotinic receptor-mediated neuroprotection of dopaminergic neurons in a mouse Parkinson's disease model.
The objective of the present study was to explore the potential functions of α7-nAChRs in PD pathology, and to determine whether these effects are exerted via Wnt/β-catenin signaling in a mouse PD model. In the in vivo study, α7-nAChR knockout (α7-KO) reversed the beneficial effects of nicotine on motor deficits, dopaminergic neuron loss, astrocyte and microglia activation, and reduced striatal dopamine release induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Injury to SH-SY5Y cells by 1-methyl-4-phenylpyridinium treatment was also ameliorated by nicotine, and this effect was abolished by methyllycaconitine (ML...
Source: Biochemical Pharmacology - May 24, 2017 Category: Drugs & Pharmacology Authors: Liu Y, Hao S, Yang B, Fan Y, Qin X, Chen Y, Hu J Tags: Biochem Pharmacol Source Type: research

Nanotechnology As Potential Tool for siRNA Delivery in Parkinson's Disease.
Abstract The lack of an outright treatment for Parkinson's disease (PD) is a pivotal concern in medicine and has driven the search for novel alternatives for treating the disease. Among the proposed approaches, small interfering RNA (siRNA)-based therapy is attracting significant attention as a potential method for the treatment of PD; however, siRNAs delivery possesses potential drawbacks, such as reduced stability in blood circulation and low capacity for reaching the target site. Therefore, siRNA delivery to the brain is a key issue that remains unsolved to date. In this regard, nanoparticles are being develope...
Source: Current Drug Targets - March 21, 2017 Category: Drugs & Pharmacology Authors: Cortés H, Alcalá-Alcalá S, Ávalos-Fuentes A, Mendoza-Muñoz N, Quintanar-Guerrero D, Leyva-Gómez G, Florán B Tags: Curr Drug Targets Source Type: research

RGS2 modulates the activity and internalization of dopamine D2 receptors in neuroblastoma N2A cells.
Abstract Dysregulated expression and function of dopamine D2 receptors (D2Rs) are implicated in drug addiction, Parkinson's disease and schizophrenia. In the current study, we examined whether D2Rs are modulated by regulator of G protein signaling 2 (RGS2), a member of the RGS family that regulates G protein signaling via acceleration of GTPase activity. Using neuroblastoma 2a (N2A) cells, we found that RGS2 was immunoprecipitated by aluminum fluoride-activated Gαi2 proteins. RGS2 siRNA knockdown enhanced membrane [(35)S] GTPγS binding to activated Gαi/o proteins, augmented inhibition of cAMP accumulation and i...
Source: Neuropharmacology - August 11, 2016 Category: Drugs & Pharmacology Authors: Luessen DJ, Hinshaw TP, Sun H, Howlett AC, Marrs G, McCool BA, Chen R Tags: Neuropharmacology Source Type: research

20C, a bibenzyl compound isolated from Gastrodia elata, protects PC12 cells against rotenone-induced apoptosis via activation of the Nrf2/ARE/HO-1 signaling pathway.
CONCLUSION: The bibenzyl compound 20C protects PC12 cells from rotenone-induced apoptosis, at least in part, via activation of the Nrf2/ARE/HO-1 signaling pathway. PMID: 27180985 [PubMed - as supplied by publisher]
Source: Acta Pharmacologica Sinica - May 15, 2016 Category: Drugs & Pharmacology Authors: Huang JY, Yuan YH, Yan JQ, Wang YN, Chu SF, Zhu CG, Guo QL, Shi JG, Chen NH Tags: Acta Pharmacol Sin Source Type: research

Prevention of the degeneration of human dopaminergic neurons in an astrocyte co‐culture system allowing endogenous drug metabolism
Conclusions and ImplicationsOur new model system is a closer model of human brain tissue than conventional cultures. Its use for screening of candidate neuroprotectants may increase the predictiveness of a test battery.
Source: British Journal of Pharmacology - June 26, 2015 Category: Drugs & Pharmacology Authors: Liudmila Efremova, Stefan Schildknecht, Martina Adam, Regina Pape, Simon Gutbier, Benjamin Hanf, Alexander Bürkle, Marcel Leist Tags: RESEARCH PAPER Source Type: research

Naringenin protects against 6-OHDA-induced neurotoxicity via activation of the Nrf2/ARE signaling pathway.
Abstract There is increasing evidence that oxidative stress is critically involved in the pathogenesis of Parkinson's disease (PD), suggesting that pharmacological targeting of the antioxidant machinery may have therapeutic value. Naringenin, a natural flavonoid compound, has been reported to possess neuroprotective effect against PD related pathology; however the mechanisms underlying its beneficial effects are poorly defined. Thus, the purpose of the present study was to investigate the potential neuroprotective role of naringenin and to delineate its mechanism of action against 6-hydroxydopamine (6-OHDA)-induce...
Source: Neuropharmacology - December 10, 2013 Category: Drugs & Pharmacology Authors: Lou H, Jing X, Wei X, Shi H, Ren D, Zhang X Tags: Neuropharmacology Source Type: research

Cathepsin X promotes 6-hydroxydopamine-induced apoptosis of PC12 and SH-SY5Y cells.
Abstract The cysteine carboxypeptidase cathepsin X is an important player in degenerative processes under normal aging and pathological conditions. In the present study, we investigated the potential role of cathepsin X in 6-hydroxydopamine (6-OHDA)-induced toxicity in the pheochromocytoma cell line PC12 and neuroblastoma cell line SH-SY5Y. Cells exposed to 6-OHDA demonstrated alterations in the protein level of cathepsin X and activity of cathepsin X. Downregulation of cathepsin X expression by siRNA attenuated the neuronal death caused by 6-OHDA. Treatment with specific cathepsin X inhibitor AMS36 protected cell...
Source: Neuropharmacology - August 16, 2013 Category: Drugs & Pharmacology Authors: Pišlar AH, Zidar N, Kikelj D, Kos J Tags: Neuropharmacology Source Type: research

Colchicine protects dopaminergic neurons in a rat model of Parkinson's disease.
Abstract A key feature of Parkinson's disease is the dopaminergic neuronal cell loss in the substantia nigra pars compacta. Besides inflammation, oxidative stress and apoptosis, a recent hypothesis suggested that degeneration of dopaminergic neurons occurs secondary to abnormal mitosis in these 'postmitotic neurons', ending up in apoptosis. Hence, recent therapies tried to prevent this mitotic cycle in dopaminergic neurons. However, most of the advocated therapies e.g., siRNA-induced silencing of cell cycle regulators, seems far from clinical application. In consequence, the use of anti-mitotic drugs could be a mo...
Source: CNS and Neurological Disorders Drug Targets - November 1, 2012 Category: Drugs & Pharmacology Authors: Salama M, Ellaithy A, Helmy B, El-Gamal M, Tantawy D, Mohamed M, Sheashaa H, Sobh M, Arias-Carrion O Tags: CNS Neurol Disord Drug Targets Source Type: research

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