کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4932518 1433523 2018 34 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Parkin absence accelerates microtubule aging in dopaminergic neurons
ترجمه فارسی عنوان
غفلت پارکینس، پیری میکروتوبول ها را در نورونهای دوپامینی ارگانیک افزایش می دهد
کلمات کلیدی
میکروتوبول، تغییرات پس از ترجمه توبولین، پارکین، بیماری پارکینسون، سالخورده، نورونهای دوپامینرژیک،
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
چکیده انگلیسی
Loss-of-function caused by mutations in the parkin gene (PARK2) lead to early-onset familial Parkinson's disease. Recently, mechanistic studies proved the ability of parkin in regulating mitochondria homeostasis and microtubule (MT) stability. Looking at these systems during aging of PARK2 knockout mice, we found that loss of parkin induced an accelerated (over)acetylation of MT system both in dopaminergic neuron cell bodies and fibers, localized in the substantia nigra and corpus striatum, respectively. Interestingly, in PARK2 knockout mice, changes of MT stability preceded the alteration of mitochondria transport. Moreover, in-cell experiments confirmed that loss of parkin affects mitochondria mobility and showed that this defect depends on MT system as it is rescued by paclitaxel, a well-known MT-targeted agent. Furthermore, both in PC12 neuronal cells and in patients' induced pluripotent stem cell-derived midbrain neurons, we observed that parkin deficiencies cause the fragmentation of stable MTs. Therefore, we suggest that parkin acts as a regulator of MT system during neuronal aging, and we endorse the hypothesis that MT dysfunction may be crucial in the pathogenesis of Parkinson's disease.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Aging - Volume 61, January 2018, Pages 66-74
نویسندگان
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