کد مقاله کد نشریه سال انتشار مقاله انگلیسی ترجمه فارسی نسخه تمام متن
5548695 1402841 2018 9 صفحه PDF سفارش دهید دانلود کنید
عنوان انگلیسی مقاله
Valproic acid and its congener propylisopropylacetic acid reduced the amount of soluble amyloid-β oligomers released from 7PA2 cells
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب رفتاری
پیش نمایش صفحه اول مقاله
Valproic acid and its congener propylisopropylacetic acid reduced the amount of soluble amyloid-β oligomers released from 7PA2 cells
چکیده انگلیسی


- Valproic acid (VPA) and propylisopropylacetic acid (PIA) affect soluble Aβ species in 7PA2 cells.
- VPA and PIA reduced release of soluble Aβ oligomers from 7PA2 cells.
- VPA and PIA increased release of Aβ monomers from 7PA2 cells.
- Platelet activating factor reversed the effects of VPA and PIA on Aβ species in 7PA2 cells.

The amyloid hypothesis of Alzheimer's disease suggests that synaptic degeneration and pathology is caused by the accumulation of amyloid-β (Aβ) peptides derived from the amyloid precursor protein (APP). Subsequently, soluble Aβ oligomers cause the loss of synaptic proteins from neurons, a histopathological feature of Alzheimer's disease that correlates with the degree of dementia. In this study, the production of toxic forms of Aβ was examined in vitro using 7PA2 cells stably transfected with human APP. We show that conditioned media from 7PA2 cells containing Aβ oligomers caused synapse degeneration as measured by the loss of synaptic proteins, including synaptophysin and cysteine-string protein, from cultured neurons. Critically, conditioned media from 7PA2 cells treated with valproic acid (2-propylpentanoic acid (VPA)) or propylisopropylacetic acid (PIA) did not cause synapse damage. Treatment with VPA or PIA did not significantly affect total Aβ42 concentrations; rather these drugs selectively reduced the concentrations of Aβ42 oligomers in conditioned media. In contrast, treatment significantly increased the concentrations of Aβ42 monomers in conditioned media. VPA or PIA treatment reduced the concentrations of APP within lipid rafts, membrane compartments associated with Aβ production. These effects of VPA and PIA were reversed by the addition of platelet-activating factor, a bioactive phospholipid produced following activation of phospholipase A2, an enzyme sensitive to VPA and PIA. Collectively these data suggest that VPA and PIA reduce Aβ oligomers through inhibition of phospholipase A2 and suggest a novel therapeutic approach to Alzheimer's treatment.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuropharmacology - Volume 128, January 2018, Pages 54-62
نویسندگان
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