دورية أكاديمية
Amyloid beta dimers/trimers potently induce cofilin-actin rods that are inhibited by maintaining cofilin-phosphorylation
العنوان: | Amyloid beta dimers/trimers potently induce cofilin-actin rods that are inhibited by maintaining cofilin-phosphorylation |
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المؤلفون: | Podlisny Marcia, Minamide Laurie S, Maloney Michael T, Marsden Ian T, Davis Richard C, Selkoe Dennis J, Bamburg James R |
المصدر: | Molecular Neurodegeneration, Vol 6, Iss 1, p 10 (2011) |
بيانات النشر: | BMC |
سنة النشر: | 2011 |
المجموعة: | Directory of Open Access Journals: DOAJ Articles |
مصطلحات موضوعية: | Neurology. Diseases of the nervous system, RC346-429, Geriatrics, RC952-954.6 |
الوصف: | Background Previously we reported 1 μM synthetic human amyloid beta 1-42 oligomers induced cofilin dephosphorylation (activation) and formation of cofilin-actin rods within rat hippocampal neurons primarily localized to the dentate gyrus. Results Here we demonstrate that a gel filtration fraction of 7PA2 cell-secreted SDS-stable human Aβ dimers and trimers (Aβd/t) induces maximal neuronal rod response at ~250 pM. This is 4,000-fold more active than traditionally prepared human Aβ oligomers, which contain SDS-stable trimers and tetramers, but are devoid of dimers. When incubated under tyrosine oxidizing conditions, synthetic human but not rodent Aβ 1-42 , the latter lacking tyrosine, acquires a marked increase (620 fold for EC 50 ) in rod-inducing activity. Gel filtration of this preparation yielded two fractions containing SDS-stable dimers, trimers and tetramers. One, eluting at a similar volume to 7PA2 Aβd/t, had maximum activity at ~5 nM, whereas the other, eluting at the void volume (high-n state), lacked rod inducing activity at the same concentration. Fractions from 7PA2 medium containing Aβ monomers are not active, suggesting oxidized SDS-stable Aβ 1-42 dimers in a low-n state are the most active rod-inducing species. Aβd/t-induced rods are predominantly localized to the dentate gyrus and mossy fiber tract, reach significance over controls within 2 h of treatment, and are reversible, disappearing by 24 h after Aβd/t washout. Overexpression of cofilin phosphatases increase rod formation when expressed alone and exacerbate rod formation when coupled with Aβd/t, whereas overexpression of a cofilin kinase inhibits Aβd/t-induced rod formation. Conclusions Together these data support a mechanism by which Aβd/t alters the actin cytoskeleton via effects on cofilin in neurons critical to learning and memory. |
نوع الوثيقة: | article in journal/newspaper |
اللغة: | English |
تدمد: | 1750-1326 |
العلاقة: | http://www.molecularneurodegeneration.com/content/6/1/10Test; https://doaj.org/toc/1750-1326Test; https://doaj.org/article/1c38ae566d114627bca7b772825d386cTest |
DOI: | 10.1186/1750-1326-6-10 |
الإتاحة: | https://doi.org/10.1186/1750-1326-6-10Test https://doaj.org/article/1c38ae566d114627bca7b772825d386cTest |
رقم الانضمام: | edsbas.64D8E620 |
قاعدة البيانات: | BASE |
تدمد: | 17501326 |
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DOI: | 10.1186/1750-1326-6-10 |