Amyloid-ОІ with isomerized Asp7 cytotoxicity is coupled to protein phosphorylationстатья
Статья опубликована в высокорейтинговом журнале
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Дата последнего поиска статьи во внешних источниках: 17 апреля 2018 г.
Аннотация:Neuronal dysfunction and loss associated with the accumulation of amyloid-ОІ (AОІ) in the form of extracellular amyloid plaques and hyperphosphorylated tau in the form of intraneuronal neurofibrillary tangles represent key features of Alzheimer's disease (AD). Amyloid plaques found in the brains of AD patients are predominantly composed of AОІ42 and its multiple chemically or structurally modified isoforms. Recently, we demonstrated that AОІ42 with isomerised Asp7 (isoAОІ42) which is one of the most abundant AОІ isoform in plaques, exhibited high neurotoxicity in human neuronal cells. Here, we show that, in SH-SY5Y neuroblastoma cells, the administration of synthetic isoAОІ42 rather than intact AОІ42 resulted in a significantly higher level of protein phosphorylation, especially the phosphorylation of tau, tubulins, and matrin 3. IsoAОІ42 induced a drastic reduction of tau protein levels. Our data demonstrate, for the first time, that isoAОІ42, being to date the only known synthetic AОІ species to cause AD-like amyloidogenesis in an animal AD model, induced cell death by disabling structural proteins in a manner characteristic of that observed in the neurons of AD patients. The data emphasize an important role of isoAОІ42 in AD progression and provide possible neurotoxicity paths for this particular isoform.