a b s t r a c tHyperhomocysteinemia has recently been identified as an important risk factor for Alzheimer's disease (AD). One of the potential mechanisms underlying harmful effects of homocysteine (Hcy) is site-specific acylation of proteins at lysine residues by homocysteine thiolactone (HCTL). The accumulation of amyloid b-peptide (Ab) in the brain is a neuropathological hallmark of AD. In the present study we were interested to investigate the effects of N-homocysteinylation on the aggregation propensity and neurotoxicity of Ab 1-42 . By coupling several techniques, we demonstrated that the homocysteinylation of lysine residues increase the neurotoxicity of the Ab peptide by stabilizing soluble oligomeric intermediates.
Structured summary of protein interactions:A Beta 1-42 and A Beta 1-42 bind by fluorescence technology (View interaction) A Beta 1-42 and A Beta 1-42 bind by electron microscopy (View interaction)
Human induced pluripotent stem cells (hiPSCs) are attractive sources of cells for disease modeling in vitro, and they may eventually provide access to cells/tissues for the treatment of many degenerative diseases. Stepwise differentiation from hiPSCs to definitive endoderm (DE) will identify a key step in hepatocytes and beta cell development and may prove useful for transplantation therapy for liver diseases and diabetes. Inducer of definitive endoderm 1 (IDE1) is known to play an important role in the regional specification of DE. Here, we have investigated the effect of stimulation with IDE1 on the development of hiPSCs into DE cells in three-dimensional (3D) cultures. The differentiation was determined by immunofluorescence staining with Sox17, FoxA2, and goosecoid (Gsc) and also by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) analysis. In this study, we showed that hiPSCs with 6-day IDE1 treatment (as chemical tool) on poly(ε-caprolactone) (PCL) nanofibrous scaffold were able to differentiate into DE cells.
Edited by Jesus Avila
Keywords:Tau protein (4R/1N) Microtubule protein Homocysteine thiolactone N-Homocysteinylation a b s t r a c t Tau isoforms promote neuronal integrity through binding and stabilization of microtubule proteins (MTP). It has been shown that hyperphosphorylation of tau contributes to Alzheimer's disease (AD) pathology and related tauopathies. However, other pathogenic modifications of tau have not been well characterized. It is well accepted that elevated level of homocysteine (Hcy) is associated with neurodegenerative diseases such as AD. As a result of N-homocysteinylation of lysine residues, Hcy becomes a component of proteins, as a protein-homocystamide adduct, which affects protein structure and function. Here we demonstrate that N-homocysteinylation of human tau (4R/1N isoform) inhibits its function via impaired tau-tubulin specific binding and MTP assembly dynamics in vitro.
a b s t r a c tStructural integrity of microtubule protein (MTP) is pivotal for its physiological roles. Disruption of the MTP network is known to be involved in neurodegenerative disorders. The gum resin of plants of the boswellia species, with b-boswellic acid (BBA) as the major component, has long been used in Ayurveda and Oriental Medicine to prevent amnesia. In the current study, we addressed the question whether BBA affects assembly dynamics behavior of tubulin. Our in vitro results revealed that BBA increases MTP length distribution and the polymerization rate of tubulin, moderately stabilizing it and diminishing both the critical concentration (C c ) and the fraction of inactive tubulin (F i ).
Cellular protein degradation systems are necessary to avoid the accumulation of misfolded or damaged proteins. Deficiency in these systems might cause to partial degradation of misfolded proteins and generation of amyloidogenic fragments. Protein misfolding is believed to be the primary cause of neurodegenerative disorders such as Alzheimer's disease (AD). In this study, we investigate effect of two anionic peptide fragments including, an acidic fragment of human Aβ (Aβ1-11) and a phosphorylated fragment of β-Casein (Tetraphosphopeptide), on tau protein aggregation. According to our results, these peptide fragments, induced tau fibrillization in vitro. In sum, we suggest that structural and conformational characters of inducer are as important as charge distribution on anionic inducer molecules however more experiments would be need to exactly confirm this suggestion.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.