کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4323691 1613808 2016 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Fasudil, a Rho kinase inhibitor, promotes the autophagic degradation of A53T α-synuclein by activating the JNK 1/Bcl-2/beclin 1 pathway
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
Fasudil, a Rho kinase inhibitor, promotes the autophagic degradation of A53T α-synuclein by activating the JNK 1/Bcl-2/beclin 1 pathway
چکیده انگلیسی


• A53T α-synuclein could decrease neurite outgrowth with enhanced Rho kinase activity.
• Fasudil could attenuate the neurite outgrowth injury caused by A53T α-synuclein.
• Fasudil could promote the autophagic degradation of A53T α-synuclein.
• The effect of fasudil was mediated by JNK/Bcl-2/beclin 1/Vps34 pathway.

Accumulation of α-synuclein (α-syn) is pivotally implicated in the pathogenesis of Parkinson׳s disease (PD), and enhancing its clearance might be a promising strategy in PD treatment. It has recently been shown that Rho kinase (ROCK) activation is involved in many neurodegenerative diseases, and some ROCK inhibitors might promote the degradation of abnormal protein aggregates. However, it is not known if fasudil, the only ROCK inhibitor available in clinical setting, could promote the degradation of α-syn, and ameliorate the α-syn induced neurotoxicity. In this regard, we investigated the effect of fasudil on neurite injury caused by A53T α-syn overexpression and the implicated pathway it might mediate. In the current study, we found that under the condition of A53T α-syn overexpression, the neurite outgrowth decreased significantly with the increasing expression of ROCK2. Fasudil, the ROCK inhibitor, ameliorated such neurotoxicity and promoted the clearance of A53T α-syn. Its underlying mechanism was supported by that fasudil could increase the macroautophagy activation via JNK 1 and Bcl-2 phosphorylation and beclin 1/Vps34 complex formation. Taken together, fasudil might be able to provide a novel and promising strategy for PD treatment by enhancing α-syn clearance and activating the JNK 1/Bcl-2/beclin 1 pathway.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Brain Research - Volume 1632, 1 February 2016, Pages 9–18
نویسندگان
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