کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
8841485 1615022 2018 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Supratherapeutic concentrations of cilostazol inhibits β-amyloid oligomerization in vitro
کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
Supratherapeutic concentrations of cilostazol inhibits β-amyloid oligomerization in vitro
چکیده انگلیسی
Alzheimer disease (AD) is the most common type of dementia, and is currently incurable. The efficacy of existing treatments for AD such as acetylcholinesterase inhibitors is limited to symptom improvement. Research on disease-modifying therapies (DMTs) has conventionally focused on amelioration of CNS pathogenesis. Two neuropathological changes correlate strongly with AD, the appearance of neurofibrillary tangles containing the microtubule-associated protein tau and extracellular amyloid deposits containing amyloid β-protein (Aβ). The aggregation of Aβ is believed to be the key pathogenic event in AD, with oligomeric assemblies thought to be the most neurotoxic form. Inhibitors of oligomer formation, therefore, could be valuable therapeutics for AD patients. The clinical phosphodiesterase type-3 inhibitor cilostazol (CSZ) was recently found to suppress the progression of cognitive decline in patients with stable AD receiving acetylcholinesterase inhibitors. Here we examined the effects of CSZ on in vitro aggregations of Aβ1-40 and Aβ1-42 including oligomerization, using the thioflavin T assay, photo-induced cross-linking of unmodified proteins, and electron microscopy. CSZ (25-100 μM) inhibited Aβ aggregation, especially oligomer formation. Considering that CSZ might be a key molecule for DMTs of AD, it cannot be ruled out that the low concentration of CSZ achievable in patient dosing may display some ant-oligomeric activity in synergy with its known therapeutic effects.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience Letters - Volume 677, 11 June 2018, Pages 19-25
نویسندگان
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