کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1921087 1048758 2009 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
A chemical chaperone, sodium 4-phenylbutyric acid, attenuates the pathogenic potency in human α-synuclein A30P + A53T transgenic mice
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
پیش نمایش صفحه اول مقاله
A chemical chaperone, sodium 4-phenylbutyric acid, attenuates the pathogenic potency in human α-synuclein A30P + A53T transgenic mice
چکیده انگلیسی

Aggregation and cytotoxicity of misfolded α-synuclein are postulated to be crucial in the disease processes of Parkinson's disease (PD) and other synucleinopathies. Mutations in the α-synuclein gene in some pedigrees of familial PD have been reported. The mutant α-synuclein has been reported to form fibrillar aggregates resulting in biochemical abnormalities that are responsible for the onset of familial PD. Thus, any agent that effectively prevents the development of misfolded and aggregated α-synuclein would be a disease modifying therapeutic candidate. We examined the efficacy of sodium 4-phenylbutyric acid (PBA), one of the chemical chaperons, in transgenic (Tg) mice overexpressing human α-synuclein containing a double mutation (A30P + A53T). To evaluate the therapeutic efficacy, bradykinesia and motor coordination were assessed using a pole test and a rotarod treadmill task, respectively. After PBA treatment, these motor deteriorations gradually improved. In immunohistochemical examinations, both a loss of tyrosine hydroxylase-positive neurons and an increase of phosphorylated α-synuclein in the substantia nigra were inhibited, resulting in no depletion of the striatal dopamine content. These data suggest that PBA might be one of the therapeutic reagents for neurodegenerative disorders.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Parkinsonism & Related Disorders - Volume 15, Issue 9, 5 November 2009, Pages 649–654
نویسندگان
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