scholarly journals Pulsed Telecommunication Signals of Non-ionizing Radiation Affect Amyloid Precursor Protein and α-Synuclein Metabolism in Non-neural Human Cells

2020 ◽  
Author(s):  
AIKATERINA STEFI ◽  
KATERINA SKOUROLIAKOU ◽  
LUKAS MARGARITIS ◽  
DIDO VASSILACOPOULOU
Keyword(s):  
Amyloid Precursor Protein ◽  
Alpha Synuclein ◽  
Human Cells ◽  
Precursor Protein ◽  
Whole Body ◽  
Neural Cells ◽  
Telecommunications Network ◽  
App Metabolism ◽  
Living Organisms

The expanding use of devices emitting Pulsed Telecommunication Signals (PTS) has launched a serious debate over the possible effects of electromagnetic radiation (EMR) on living organisms. Our previous work has indicated that PTS exposure alters Amyloid Precursor Protein (APP) and alpha-synuclein (α-syn) metabolism in human cells of neural origin, providing a possible connection between exposure and neurodegeneration. This investigation aimed to reveal, in vitro in human non-neural cells (HEK293), the aftermath of the same exposure on the processing of APP and α-syn. Data presented here, indicate changes in APP metabolism, acquisition of different cellular topologies of the newly generated APP fragments, changes in monomeric α-syn accumulation and multimerization, indicating that APP and α-syn processing is possibly altered in the periphery by EMR. These effects are accompanied by a substantial increase in the levels of Reactive Oxygen Species (ROS). Further investigation is required in order to provide insights into the interaction of PTS with non-neural cells affecting the peripheral systemic functional stability. This is necessary because nowadays whole body human exposure from various EMR sources is a fact in normal life with the valid estimation that they may be increased in view of the forthcoming 5G telecommunications network implementation.

scholarly journals Nitrous Oxide Plus Isoflurane Induces Apoptosis and Increases β-Amyloid Protein Levels

2009 ◽  
Vol 111 (4) ◽  
pp. 741-752 ◽  
Author(s):  
Yu Zhen ◽  
Yuanlin Dong ◽  
Xu Wu ◽  
Zhipeng Xu ◽  
Yan Lu ◽  
...  
Keyword(s):  
Nitrous Oxide ◽  
Amyloid Precursor Protein ◽  
Caspase 3 ◽  
Precursor Protein ◽  
Primary Neurons ◽  
Gamma Secretase ◽  
Protein Levels ◽  
Secretase Inhibitor

Background Some anesthetics have been suggested to induce neurotoxicity, including promotion of Alzheimer's disease neuropathogenesis. Nitrous oxide and isoflurane are common anesthetics. The authors set out to assess the effects of nitrous oxide and/or isoflurane on apoptosis and beta-amyloid (Abeta) levels in H4 human neuroglioma cells and primary neurons from naïve mice. Methods The cells or neurons were exposed to 70% nitrous oxide and/or 1% isoflurane for 6 h. The cells or neurons and conditioned media were harvested at the end of the treatment. Caspase-3 activation, apoptosis, processing of amyloid precursor protein, and Abeta levels were determined. Results Treatment with a combination of 70% nitrous oxide and 1% isoflurane for 6 h induced caspase-3 activation and apoptosis in H4 naïve cells and primary neurons from naïve mice. The 70% nitrous oxide plus 1% isoflurane, but neither alone, for 6 h induced caspase-3 activation and apoptosis, and increased levels of beta-site amyloid precursor protein-cleaving enzyme and Abeta in H4-amyloid precursor protein cells. In addition, the nitrous oxide plus isoflurane-induced Abeta generation was reduced by a broad caspase inhibitor, Z-VAD. Finally, the nitrous oxide plus isoflurane-induced caspase-3 activation was attenuated by gamma-secretase inhibitor L-685,458, but potentiated by exogenously added Abeta. Conclusion These results suggest that the common anesthetics nitrous oxide plus isoflurane may promote neurotoxicity by inducing apoptosis and increasing Abeta levels. The generated Abeta may further potentiate apoptosis to form another round of apoptosis and Abeta generation. More studies, especially the in vivo confirmation of these in vitro findings, are needed.

The Absence of Myelin Basic Protein Reduces Non-Amyloidogenic Processing of Amyloid Precursor Protein

2021 ◽  
Vol 18 ◽  
Author(s):  
Chika Seiwa ◽  
Ichiro Sugiyama ◽  
Makoto Sugawa ◽  
Hiroaki Murase ◽  
Chiaki Kudoh ◽  
...  
Keyword(s):  
Amyloid Precursor Protein ◽  
Myelin Basic Protein ◽  
Basic Protein ◽  
Amyloid Β ◽  
Precursor Protein ◽  
Amyloid Β Protein ◽  
Pathological Feature ◽  
Novel Therapy ◽  
App Processing ◽  
App Metabolism

Background: The accumulation of amyloid β-protein (Aβ) in the brain is a pathological feature of Alzheimer’s disease (AD). Aβ peptides originate from amyloid precursor protein (APP). APP can be proteolytically cleaved through amyloidogenic or non-amyloidogenic pathways. The molecular effects on APP metabolism / processing may be influenced by myelin and the breakdown of myelin basic protein (MBP) in AD patients and mouse models of AD pathology. Methods: We directly tested whether MBP can alter influence APP processing in MBP-/- mice, known as Shiverer (shi/shi) mice, in which no functional MBP is produced due to gene breakage from the middle of MBP exon II. Results: A significant reduction of the cerebral sAPPα level in Shiverer (shi/shi) mice was found, although the levels of both total APP and sAPPβ remain unchanged. The reduction of sAPPα was considered to be due to the changes in the expression levels of a disintegrin and metalloproteinase-9 (ADAM9) catalysis and non-amyloid genic processing of APP in the absence of MBP because it binds to ADAM9. MBP -/- mice exhibited increased Aβ oligomer production. Conclusion: Together, these findings suggest that in the absence of MBP, there is a marked reduction of non-amyloidogenic APP processing to sAPPα, and targeting myelin of oligodendrocytes may be a novel therapy for the prevention and treatment of AD.

scholarly journals SPON1 Can Reduce Amyloid Beta and Reverse Cognitive Impairment and Memory Dysfunction in Alzheimer’s Disease Mouse Model

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1275
Author(s):  
Soo Yong Park ◽  
Joo Yeong Kang ◽  
Taehee Lee ◽  
Donggyu Nam ◽  
Chang-Jin Jeon ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Amyloid Precursor Protein ◽  
Amyloid Beta ◽  
Physiological Activity ◽  
Precursor Protein ◽  
Age Related

Alzheimer’s disease (AD) is a complex, age-related neurodegenerative disease that is the most common form of dementia. However, the cure for AD has not yet been founded. The accumulation of amyloid beta (Aβ) is considered to be a hallmark of AD. Beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), also known as beta secretase is the initiating enzyme in the amyloidogenic pathway. Blocking BACE1 could reduce the amount of Aβ, but this would also prohibit the other functions of BACE1 in brain physiological activity. SPONDIN1 (SPON1) is known to bind to the BACE1 binding site of the amyloid precursor protein (APP) and blocks the initiating amyloidogenesis. Here, we show the effect of SPON1 in Aβ reduction in vitro in neural cells and in an in vivo AD mouse model. We engineered mouse induced neural stem cells (iNSCs) to express Spon1. iNSCs harboring mouse Spon1 secreted SPON1 protein and reduced the quantity of Aβ when co-cultured with Aβ-secreting Neuro 2a cells. The human SPON1 gene itself also reduced Aβ in HEK 293T cells expressing the human APP transgene with AD-linked mutations through lentiviral-mediated delivery. We also demonstrated that injecting SPON1 reduced the amount of Aβ and ameliorated cognitive dysfunction and memory impairment in 5xFAD mice expressing human APP and PSEN1 transgenes with five AD-linked mutations.

scholarly journals Presenilin 1 Controls γ-Secretase Processing of Amyloid Precursor Protein in Pre-Golgi Compartments of Hippocampal Neurons

1999 ◽  
Vol 147 (2) ◽  
pp. 277-294 ◽  
Author(s):  
Wim G. Annaert ◽  
Lyne Levesque ◽  
Kathleen Craessaerts ◽  
Inge Dierinck ◽  
Greet Snellings ◽  
...  
Keyword(s):  
Subcellular Localization ◽  
Amyloid Precursor Protein ◽  
Hippocampal Neurons ◽  
Subcellular Fractionation ◽  
Precursor Protein ◽  
Presenilin 1 ◽  
Carboxy Terminal ◽  
Endocytic Pathways

Mutations of presenilin 1 (PS1) causing Alzheimer's disease selectively increase the secretion of the amyloidogenic βA4(1-42), whereas knocking out the gene results in decreased production of both βA4(1-40) and (1-42) amyloid peptides (De Strooper et al. 1998). Therefore, PS1 function is closely linked to the γ-secretase processing of the amyloid precursor protein (APP). Given the ongoing controversy on the subcellular localization of PS1, it remains unclear at what level of the secretory and endocytic pathways PS1 exerts its activity on APP and on the APP carboxy-terminal fragments that are the direct substrates for γ-secretase. Therefore, we have reinvestigated the subcellular localization of endogenously expressed PS1 in neurons in vitro and in vivo using confocal microscopy and fine-tuned subcellular fractionation. We show that uncleaved PS1 holoprotein is recovered in the nuclear envelope fraction, whereas the cleaved PS fragments are found mainly in post-ER membranes including the intermediate compartment (IC). PS1 is concentrated in discrete sec23p- and p58/ERGIC-53–positive patches, suggesting its localization in subdomains involved in ER export. PS1 is not found to significant amounts beyond the cis-Golgi. Surprisingly, we found that APP carboxy-terminal fragments also coenrich in the pre-Golgi membrane fractions, consistent with the idea that these fragments are the real substrates for γ-secretase. Functional evidence that PS1 exerts its effects on γ-secretase processing of APP in the ER/IC was obtained using a series of APP trafficking mutants. These mutants were investigated in hippocampal neurons derived from transgenic mice expressing PS1wt or PS1 containing clinical mutations (PS1M146L and PS1L286V) at physiologically relevant levels. We demonstrate that the APP-London and PS1 mutations have additive effects on the increased secretion of βA4(1-42) relative to βA4(1-40), indicating that both mutations operate independently. Overall, our data clearly establish that PS1 controls γ42-secretase activity in pre-Golgi compartments. We discuss models that reconcile this conclusion with the effects of PS1 deficiency on the generation of βA4(1-40) peptide in the late biosynthetic and endocytic pathways.

AMYLOID PRECURSOR PROTEIN IN CULTURED HUMAN CELLS

1988 ◽  
Vol 2 (4) ◽  
pp. 402
Author(s):  
KOVACS D ◽  
MORANDI A ◽  
TABATON M ◽  
PERRY G ◽  
MASTER C ◽  
...  
Keyword(s):  
Amyloid Precursor Protein ◽  
Human Cells ◽  
Precursor Protein ◽  
Cultured Human Cells

Racemic N1-Norphenserine and Its Enantiomers: Unpredicted Inhibition of Human Acetyl- and Butyrylcholinesterase and β-Amyloid Precursor Protein in vitro

Heterocycles ◽  
2003 ◽  
Vol 61 (1) ◽  
pp. 529 ◽  
Author(s):  
Nigel H. Greig ◽  
Qian-sheng Yu ◽  
Weiming Luo ◽  
Harold W. Holloway ◽  
Tada Utsuki ◽  
...  
Keyword(s):  
Amyloid Precursor Protein ◽  
Precursor Protein ◽  
Β Amyloid

scholarly journals Modification of lipid rafts by extracellular vesicles carrying HIV-1 protein Nef induces redistribution of amyloid precursor protein and Tau, causing neuronal dysfunction

2020 ◽  
Vol 295 (38) ◽  
pp. 13377-13392
Author(s):  
Michael Ditiatkovski ◽  
Nigora Mukhamedova ◽  
Dragana Dragoljevic ◽  
Anh Hoang ◽  
Hann Low ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Amyloid Precursor Protein ◽  
Brain Tissue ◽  
Lipid Rafts ◽  
Extracellular Vesicles ◽  
Plasma Membranes ◽  
Precursor Protein ◽  
Short Term Treatment ◽  
Hiv 1

HIV-associated neurocognitive disorders (HANDs) are a frequent outcome of HIV infection. Effective treatment of HIV infection has reduced the rate of progression and severity but not the overall prevalence of HANDs, suggesting ongoing pathological process even when viral replication is suppressed. In this study, we investigated how HIV-1 protein Nef secreted in extracellular vesicles (exNef) impairs neuronal functionality. ExNef were rapidly taken up by neural cells in vitro, reducing the abundance of ABC transporter A1 (ABCA1) and thus cholesterol efflux and increasing the abundance and modifying lipid rafts in neuronal plasma membranes. ExNef caused a redistribution of amyloid precursor protein (APP) and Tau to lipid rafts and increased the abundance of these proteins, as well as of Aβ42. ExNef further potentiated phosphorylation of Tau and activation of inflammatory pathways. These changes were accompanied by neuronal functional impairment. Disruption of lipid rafts with cyclodextrin reversed the phenotype. Short-term treatment of C57BL/6 mice with either purified recombinant Nef or exNef similarly resulted in reduced abundance of ABCA1 and elevated abundance of APP in brain tissue. The abundance of ABCA1 in brain tissue of HIV-infected human subjects diagnosed with HAND was lower, and the abundance of lipid rafts was higher compared with HIV-negative individuals. Levels of APP and Tau in brain tissue correlated with the abundance of Nef. Thus, modification of neuronal cholesterol trafficking and of lipid rafts by Nef may contribute to early stages of neurodegeneration and pathogenesis in HAND.

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