14‐3‐3 protein beta isoform is associated with 3‐repeat tau neurofibrillary tangles in Alzheimer's disease

Sugimori, Kaoru; Kobayashi, Kanako; Kitamura, Tatsuru; Sudo, Satoru; Koshino, Yoshifumi

doi:10.1111/j.1440-1819.2007.01631.x

Cited by 16 publications

(11 citation statements)

References 35 publications

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“…Among them, YWHAZ is the most extensively studied, its polymorphism is associated with AD [126], [127], and it can stimulate tau phosphorylation by GSK3B [128]. In addition, YWHAB is associated with the development of the 3-repeat NFT in AD [129], and YWHAQ can mediate tau phosphorylation by SGK1 [130]. 14-3-3 proteins were significantly down-regulated at the “intermediate” and late stages.…”

Section: Discussionmentioning

confidence: 99%

Concerted Perturbation Observed in a Hub Network in Alzheimer’s Disease

et al. 2012

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Alzheimer’s disease (AD) is a progressive neurodegenerative disease involving the alteration of gene expression at the whole genome level. Genome-wide transcriptional profiling of AD has been conducted by many groups on several relevant brain regions. However, identifying the most critical dys-regulated genes has been challenging. In this work, we addressed this issue by deriving critical genes from perturbed subnetworks. Using a recent microarray dataset on six brain regions, we applied a heaviest induced subgraph algorithm with a modular scoring function to reveal the significantly perturbed subnetwork in each brain region. These perturbed subnetworks were found to be significantly overlapped with each other. Furthermore, the hub genes from these perturbed subnetworks formed a connected hub network consisting of 136 genes. Comparison between AD and several related diseases demonstrated that the hub network was robustly and specifically perturbed in AD. In addition, strong correlation between the expression level of these hub genes and indicators of AD severity suggested that this hub network can partially reflect AD progression. More importantly, this hub network reflected the adaptation of neurons to the AD-specific microenvironment through a variety of adjustments, including reduction of neuronal and synaptic activities and alteration of survival signaling. Therefore, it is potentially useful for the development of biomarkers and network medicine for AD.

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Section: Discussionmentioning

confidence: 99%

Concerted Perturbation Observed in a Hub Network in Alzheimer’s Disease

et al. 2012

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“…The other primary co-downregulated protein identified between the cortex and hippocampus was the diazepam binding inhibitor protein (DBI). DBI was first isolated from rat and human brain, and is found almost exclusively in GABAergic neurons where it is believed to inhibit GABAergic neurotransmission [31]. DBI has been proposed to block the binding of endogenous benzodiazepines (endozepines) to the regulatory site present on the GABA A receptor, thus reducing the regulation of the chloride channel current.…”

Section: Discussionmentioning

confidence: 99%

iTRAQ Analysis of Complex Proteome Alterations in 3xTgAD Alzheimer's Mice: Understanding the Interface between Physiology and Disease

et al. 2008

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Alzheimer's disease (AD) is characterized by progressive cognitive impairment associated with accumulation of amyloid β-peptide, synaptic degeneration and the death of neurons in the hippocampus, and temporal, parietal and frontal lobes of the cerebral cortex. Analysis of postmortem brain tissue from AD patients can provide information on molecular alterations present at the end of the disease process, but cannot discriminate between changes that are specifically involved in AD versus those that are simply a consequence of neuronal degeneration. Animal models of AD provide the opportunity to elucidate the molecular changes that occur in brain cells as the disease process is initiated and progresses. To this end, we used the 3xTgAD mouse model of AD to gain insight into the complex alterations in proteins that occur in the hippocampus and cortex in AD. The 3xTgAD mice express mutant presenilin-1, amyloid precursor protein and tau, and exhibit AD-like amyloid and tau pathology in the hippocampus and cortex, and associated cognitive impairment. Using the iTRAQ stable-isotope-based quantitative proteomic technique, we performed an in-depth proteomic analysis of hippocampal and cortical tissue from 16 month old 3xTgAD and non-transgenic control mice. We found that the most important groups of significantly altered proteins included those involved in synaptic plasticity, neurite outgrowth and microtubule dynamics. Our findings have elucidated some of the complex proteome changes that occur in a mouse model of AD, which could potentially illuminate novel therapeutic avenues for the treatment of AD and other neurodegenerative disorders.

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“…It is supposed that serving as an adapter 14‐3‐3, stimulates tau phosphorylation by a number of different protein kinases [6,9–11]. 14‐3‐3 promotes aggregation of unphosphorylated tau [11–13] and is presented in neurofibrillar tangles in Alzheimer's disease [14,15]. The recent data indicate that phosphorylation by protein kinase A (PKA) or protein kinase B (PKB) increases the interaction of tau with 14‐3‐3 and modifies the effect of 14‐3‐3 on tau aggregation [12,13,16].…”

Section: Introductionmentioning

confidence: 99%