Search results for "PLP"
showing 10 items of 12 documents
Structure and Synaptic Function of Metal Binding to the Amyloid Precursor Protein and its Proteolytic Fragments
2017
Alzheimer’s disease (AD) is ultimately linked to the Amyloid Precursor Protein (APP). However, current research reveals an important synaptic function of APP and APP-like proteins (APLP1 and 2). In this context various neurotrophic and neuroprotective functions have been reported for the APP proteolytic fragments sAPPα, sAPPβ, and the monomeric amyloid-beta peptide (Aβ). APP is a metalloprotein and binds copper and zinc ions. Synaptic activity correlates with a release of these ions into the synaptic cleft and dysregulation of their homeostasis is linked to different neurodegenerative diseases. Metal binding to APP or its fragments affects its structure and its proteolytic cleavage and ther…
Structural Analysis of Phosphoserine Aminotransferase (Isoform 1) From Arabidopsis thaliana– the Enzyme Involved in the Phosphorylated Pathway of Ser…
2018
Phosphoserine aminotransferase (PSAT) is a pyridoxal 5'-phosphate (PLP)-dependent enzyme that catalyzes the conversion of 3-phosphohydroxypyruvate (3-PHP) to 3-phosphoserine (PSer) in an L-glutamate (Glu)-linked reversible transamination reaction. This process proceeds through a bimolecular ping-pong mechanism and in plants takes place in plastids. It is a part of the phosphorylated pathway of serine biosynthesis, one of three routes recognized in plant organisms that yield serine. In this three-step biotransformation, 3-phosphoglycerate (3-PGA) delivered from plastidial glycolysis and Calvin cycle is oxidized by 3-PGA dehydrogenase. Then, 3-PHP is subjected to transamination with Glu to yi…
Shedding of the amyloid precursor protein-like protein APLP2 by disintegrin-metalloproteinases
2005
Cleavage of the amyloid precursor protein (APP) within the amyloid-beta (Aβ) sequence by the α-secretase prevents the formation of toxic Aβ peptides. It has been shown that the disintegrin-metalloproteinases ADAM10 and TACE (ADAM17) act as α-secretases and stimulate the generation of a soluble neuroprotective fragment of APP, APPsα. Here we demonstrate that the related APP-like protein 2 (APLP2), which has been shown to be essential for development and survival of mice, is also a substrate for both proteinases. Overexpression of either ADAM10 or TACE in HEK293 cells increased the release of neurotrophic soluble APLP2 severalfold. The strongest inhibition of APLP2 shedding in neuroblastoma c…
Amyloid Precursor-like Protein 1 Influences Endocytosis and Proteolytic Processing of the Amyloid Precursor Protein
2005
Ectodomain shedding of the amyloid precursor protein (APP) is a key regulatory step in the generation of the Alzheimer disease amyloid beta peptide (Abeta). The molecular mechanisms underlying the control of APP shedding remain little understood but are in part dependent on the low density lipoprotein receptor-related protein (LRP), which is involved in APP endocytosis. Here, we show that the APP homolog APLP1 (amyloid precursor-like protein 1) influences APP shedding. In human embryonic kidney 293 cells expression of APLP1 strongly activated APP shedding by alpha-secretase and slightly reduced beta-secretase cleavage. As revealed by domain deletion analysis, the increase in APP shedding re…
Loss of all three APP family members during development impairs synaptic function and plasticity, disrupts learning, and causes an autism-like phenot…
2021
The key role of APP for Alzheimer pathogenesis is well established. However, perinatal lethality of germline knockout mice lacking the entire APP family has so far precluded the analysis of its physiological functions for the developing and adult brain. Here, we generated conditional APP/APLP1/APLP2 triple KO (cTKO) mice lacking the APP family in excitatory forebrain neurons from embryonic day 11.5 onwards. NexCre cTKO mice showed altered brain morphology with agenesis of the corpus callosum and disrupted hippocampal lamination. Further, NexCre cTKOs revealed reduced basal synaptic transmission and drastically reduced long-term potentiation that was associated with reduced dendritic length …
Effect of transfection with PLP2 antisense oligonucleotides on gene expression of cadmium-treated MDA-MB231 breast cancer cells
2012
Emerging evidence indicates that cadmium (Cd) is able to regulate gene expression, drastically affecting the pattern of transcriptional activity in human normal and pathological cells. We have already shown that exposure of MDA-MB231 breast cancer cells to 5 μM CdCl(2) for 96 h, apart from significantly affecting mitochondrial metabolism, induces modifications of the expression level of genes coding for members of stress response-, mitochondrial respiration-, MAP kinase-, NF-κB-, and apoptosis-related pathways. In the present study, we have expanded the knowledge on the biological effects of Cd-breast cancer cell interactions, indicating PLP2 (proteolipid protein-2) as a novel member of the…
Single cell 3’UTR analysis identifies changes in alternative polyadenylation throughout neuronal differentiation and in autism
2020
SUMMARYAutism spectrum disorder (ASD) is a neurodevelopmental disease affecting social behavior. Many of the high-confident ASD risk genes relate to mRNA translation. Specifically, many of these genes are involved in regulation of gene expression for subcellular compartmentalization of proteins1. Cis-regulatory motifs that often localize to 3’- and 5’-untranslated regions (UTRs) offer an additional path for posttranscriptional control of gene expression. Alternative cleavage and polyadenylation (APA) affect 3’UTR length thereby influencing the presence or absence of regulatory elements. However, APA has not yet been addressed in the context of neurodevelopmental disorders. Here we used sing…
Saeimas atbildīgās komisijas un NEPLP locekļu naratīvs par sabiedrisko mediju lomu mediju politikā (2014.-2018. gads)
2018
Maģistra darba “Saeimas atbildīgās komisijas un NEPLP locekļu naratīvs par sabiedrisko mediju lomu mediju politikā (2014. – 2018. gads)” mērķis ir izpētīt, kādi ir lēmumu pieņēmēju naratīvi par sabiedrisko mediju lomu Latvijā. Pētījums sastāv no 4 daļām. Darba pirmajā daļā tiek apkopotas teorētiķu atziņas par sabiedrisko mediju lomu tīkla sabiedrībā, aprakstīti mediju plurālisma teorētiskie aspekti un naratīva teorija. Darba otrajā daļā tiek aprakstītas pētījumā izmantotā metodoloģiskā pieeja – naratīva analīze un datu iegūšanas metode – naratīva intervija. Darba trešajā daļā tiek izklāstīti pētījuma rezultāti. Pētījuma ceturtajā daļā tiek veikts rezultātu apkopojums un izvērsta diskusija p…
The Role of the anti-amyloidogenic secretase ADAM10 in shedding the APP-like proteins.
2011
ADAM10 (A disintegrin and metalloproteinase 10) has been demonstrated as an enzyme with protective properties in Alzheimer's disease: in mouse models it not only lowered generation of toxic A-beta peptides and formation of senile plaques but also alleviated learning deficits and enhanced synaptic density. This is due to cleavage of the amyloid precursor protein (APP) within its A-beta stretch and to the release of the extracellular domain of APP with neuroprotective function. Aside from cleaving APP, ADAM10 has been linked to over 40 putative substrates at least in cell culture. These substrates are connected with important cellular functions such as cell migration, stress response and tran…
The outcomes of national literacy programs on basic reading skills in familiar language among Zambian early graders
2016
In Zambia the Ministry of General Education implemented two national literacy programs in order to improve low levels of reading; the Primary Reading Program (PRP) implemented from 1999 to 2014 and the Primary Literacy Program (PLP) piloted in some schools in 2014 before being scaled up. This research examines the acquisition of basic reading skills among learners in familiar languages at the end of grade 2 in the two national literacy programs. I examined assessment results separately for each program and compared the two with each other. Outcomes were observed on the basis of the Early Grade Reading assessment test battery given to random samples of children (n=393) in 40 schools from 4 d…