{"id":14621,"date":"2017-05-24T13:20:45","date_gmt":"2017-05-24T13:20:45","guid":{"rendered":"https:\/\/arsco.org\/articles\/article-detail-59\/"},"modified":"2017-05-24T13:20:45","modified_gmt":"2017-05-24T13:20:45","slug":"article-detail-59","status":"publish","type":"articles","link":"https:\/\/arsco.org\/en\/articles\/article-detail-14621\/","title":{"rendered":"\u0627\u0644\u062f\u0643\u062a\u0648\u0631 \u0639\u0645\u0631 \u0639\u0644\u064a \u0627\u0644\u0623\u062c\u0646\u0641 \u0648\u0628\u062d\u0648\u062b\u0647 \u062d\u0648\u0644 \u0645\u0631\u0636 \u0627\u0644\u0628\u0627\u0631\u0643\u0646\u0633\u0648\u0646"},"content":{"rendered":"<p style=\"text-align: justify;\"><span style=\"color:#008080;\">\u0627\u0644\u0628\u0631\u0648\u0641\u064a\u0633\u0648\u0631 \u0639\u0645\u0631 \u0627\u0644\u0623\u062c\u0646\u0641 \u0648\u0644\u062f \u0641\u064a \u0644\u064a\u0628\u064a\u0627 \u0648\u062d\u0627\u0635\u0644 \u0639\u0644\u0649 \u062f\u0631\u062c\u0629 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\u0627\u0644\u0623\u062c\u0646\u0641 \u062d\u0648\u0644 \u0645\u0631\u0636 \u0627\u0644\u0628\u0627\u0631\u0643\u0646\u0633\u0648\u0646:<\/span><\/p>\n<p dir=\"ltr\">&nbsp;<\/p>\n<ul dir=\"ltr\">\n<li>Abstract 1:<\/li>\n<li><a href=\"http:\/\/www.sciencedirect.com\/science\/article\/pii\/S1525001616309984\">Molecular Therapy, 2016 Apr;24(4):746-58. doi: 10.1038\/mt.2015.232.<\/a><\/li>\n<\/ul>\n<p dir=\"ltr\">Development of Nonviral Vectors Targeting the Brain as a Therapeutic Approach for Parkinson&#39;s Disease and Other Brain Disorders.<br \/>\nParkinson&#39;s disease (PD) is a debilitating neurodegenerative disease characterized by tremor, rigidity, bradykinesia, and postural instability, for which there is no effective treatment available till date. Here, we report the development of nonviral vectors specific for neuronal cells that can deliver short interfering RNA (siRNA) against the &alpha;-synuclein gene (SNCA), and prevent PD-like symptoms both in vitro and in vivo. These vectors not only help siRNA duplexes cross the blood-brain barrier in mice, but also stabilize these siRNAs leading to a sustainable 60-90% knockdown of &alpha;-synuclein protein. Mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine rapidly develop PD-like symptoms which were significantly alleviated when SNCA was knocked down using our vectors. Together, our data not only confirm the central role of &alpha;-synuclein in the onset of PD, but also provide a proof of principle that these nonviral vectors can be used as novel tools to design effective strategies to combat central nervous system diseases.<\/p>\n<p style=\"text-align: justify;\">\u0628\u0627\u0631\u0643\u0646\u0633\u0648\u0646 \u0623\u062d\u062f \u0627\u0644\u0623\u0645\u0631\u0627\u0636 \u0627\u0644\u0645\u0631\u062a\u0628\u0637\u0629 \u0628\u062a\u0644\u0641 \u0627\u0644\u062e\u0644\u0627\u064a\u0627 \u0627\u0644\u0639\u0635\u0628\u064a\u0629 \u0648\u0645\u0646 \u0623\u0628\u0631\u0632 \u062a\u0638\u0627\u0647\u0631\u0627\u062a\u0647 \u0627\u0644\u0633\u0631\u064a\u0631\u064a\u0629: \u0627\u0644\u0631\u0651\u0639\u0627\u0634\u060c \u062a\u0635\u0644\u0651\u0628 \u0627\u0644\u0639\u0636\u0644\u0627\u062a \u0648\u0628\u0637\u0621 \u0627\u0644\u062d\u0631\u0643\u0629. \u0648\u0625\u0646\u0651\u0647 \u0644\u0645\u0646 \u0627\u0644\u0645\u0624\u0633\u0641 \u0623\u0651\u0646\u0647 \u0625\u0644\u0649 \u064a\u0648\u0645\u0646\u0627 \u0647\u0630\u0627 \u0644\u0627 \u064a\u0648\u062c\u062f \u0639\u0644\u0627\u062c \u0646\u0627\u062c\u0639 \u0644\u0644\u0645\u0631\u0636. \u0641\u064a \u0647\u0630\u0647 \u0627\u0644\u062f\u0651\u0631\u0627\u0633\u0629\u060c \u0647\u062f\u0641\u0646\u0627 \u0625\u0644\u0649 \u062a\u0637\u0648\u064a\u0631 \u0646\u0627\u0642\u0644\u0627\u062a \u063a\u064a\u0631 \u0641\u064a\u0631\u0648\u0633\u064a\u0629 \u0642\u0627\u062f\u0631\u0629 \u0639\u0644\u0649 \u062d\u0645\u0644 \u062c\u0632\u064a\u0626\u0627\u062a \u0627\u0644\u062d\u0645\u0636 \u0627\u0644\u0646\u0648\u0648\u064a \u0627\u0644\u0631\u064a\u0628\u0648\u0632\u064a \u0627\u0644\u0645\u062a\u062f\u0627\u062e\u0644\u0629 \u0627\u0644\u0635\u063a\u064a\u0631\u0629 \u062a\u0639\u0631\u0641 \u0627\u062e\u062a\u0635\u0627\u0631\u0627 (siRNA) \u0644\u062a\u062b\u0628\u064a\u0637 \u0627\u0644\u062c\u064a\u0646 \u0623\u0644\u0641\u0627 \u0633\u0646\u064a\u0648\u0643\u0644\u064a\u0646 \u0641\u064a \u0627\u0644\u062e\u0644\u0627\u064a\u0627 \u0627\u0644\u0639\u0635\u0628\u064a\u0629\u060c \u0648\u0627\u0644\u062d\u062f\u0651 \u0628\u0627\u0644\u062a\u0627\u0644\u064a \u0645\u0646 \u062a\u0638\u0627\u0647\u0631\u0627\u062a \u0628\u0627\u0631\u0643\u0646\u0633\u0648\u0646 \u0633\u0648\u0627\u0621 \u0639\u0644\u0649 \u0627\u0644\u0645\u0633\u062a\u0648\u0649 \u0627\u0644\u0645\u062e\u0628\u0631\u064a \u0623\u0648 \u0627\u0644\u062d\u064a\u0648\u064a.&nbsp; 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The identification of reliable biomarkers for disease diagnosis and progression has a key role for developing disease-modifying therapies.<\/li>\n<li>&nbsp;In this article, we investigated the longitudinal changes of CSF &alpha;-synuclein species in early PD patients and explored the potential use of these species as surrogate biomarkers for PD progression. We used our newly developed enzyme-linked immunosorbent assay systems for measuring different forms of &alpha;-synuclein, such as oligomeric-&alpha;-synuclein, phosphorylated-&alpha;-synuclein at serine 129, or total-&alpha;-synuclein in CSF from the longitudinal Deprenyl and Tocopherol Antioxidative Therapy for Parkinsonism study cohort (n = 121). CSF Alzheimer&#39;s disease biomarkers (total-tau, phosphorylated-tau, A&beta;40 , and A&beta;42 ) were also measured for this cohort.<\/li>\n<li>Interestingly, total-&alpha;-synuclein and oligomeric-&alpha;-synuclein levels significantly increased during the 2-year Deprenyl and Tocopherol Antioxidative Therapy for Parkinsonism study follow-up period, whereas phosphorylated-&alpha;-synuclein at serine 129 levels showed a longitudinal decrease. We have also noted an association between a change of the oligomeric-&alpha;-synuclein\/total-&alpha;-synuclein ratio and a worsening of motor signs, in particular in the postural-instability and gait-difficulty dominant PD group. A strong positive correlation between the changes in CSF total-&alpha;-synuclein and oligomeric-&alpha;-synuclein during the 2-year Deprenyl and Tocopherol Antioxidative Therapy for Parkinsonism study was also noted (r = 0.84, P &lt; .001). Our data show that CSF &alpha;-synuclein species have a dynamic pattern along the course of the disease, supporting their possible role as progression biomarkers for PD and their link with PD clinical phenotypes.<\/li>\n<\/ul>\n<p style=\"text-align: justify;\">&nbsp;<br \/>\n<span style=\"color:#d89e30;\">\u0627\u0644\u062a\u063a\u064a\u0651\u0631\u0627\u062a \u0627\u0644\u0637\u0651\u0648\u0644\u064a\u0629 \u0641\u064a \u0627\u0644\u0628\u0631\u0648\u062a\u064a\u0646 \u0623\u0644\u0641\u0627 \u0633\u0646\u064a\u0648\u0643\u0644\u064a\u0646 \u062a\u0631\u0635\u062f \u062a\u0637\u0651\u0648\u0631 \u0645\u0631\u0636 \u0627\u0644\u0628\u0627\u0631\u0643\u0646\u0633\u0648\u0646<\/span><\/p>\n<p style=\"text-align: justify;\">\u0644\u0627 \u0632\u0627\u0644 \u062a\u0634\u062e\u064a\u0635 \u0645\u0631\u0636 \u0628\u0627\u0631\u0643\u0646\u0633\u0648\u0646 \u0625\u0644\u0649 \u064a\u0648\u0645\u0646\u0627 \u0647\u0630\u0627 \u064a\u0639\u062a\u0645\u062f \u0639\u0644\u0649 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\u0646\u0645\u0637\u064b\u0627 \u062f\u064a\u0646\u0627\u0645\u064a\u0643\u064a\u064b\u0627 \u0639\u0628\u0631 \u062a\u0642\u062f\u0651\u0645 \u0627\u0644\u0645\u0631\u0636\u060c \u0627\u0644\u0623\u0645\u0631 \u0627\u0644\u0630\u064a \u064a\u062f\u0639\u0645 \u0625\u0645\u0643\u0627\u0646\u064a\u0629 \u062a\u0648\u0638\u064a\u0641\u0647\u0627 \u0643\u0623\u062f\u0648\u0627\u062a \u062a\u0634\u062e\u064a\u0635 \u0648\u062a\u062d\u0631\u0651\u064a \u0644\u0633\u064a\u0631 \u0645\u0631\u0636 \u0628\u0627\u0631\u0643\u0646\u0633\u0648\u0646 \u0628\u0645\u062e\u062a\u0644\u0641 \u0623\u0634\u0643\u0627\u0644\u0647 \u0627\u0644\u0633\u0631\u064a\u0631\u064a\u0629.<\/p>\n<p>&nbsp;<\/p>\n<p><span style=\"color:#d89e30;\">\u0628\u0631\u064a\u062f \u0627\u0644\u0643\u0627\u062a\u0628 \u0627\u0644\u0627\u0644\u0643\u062a\u0631\u0648\u0646\u064a<\/span>:&nbsp; <a 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