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Lipid membrane disease

Kyle I Mentkowski, Jonathan D Snitzer, Sarah Rusnak, Jennifer K Lang
Extracellular vesicles (EVs) comprise a heterogeneous group of small membrane vesicles, including exosomes, which play a critical role in intracellular communication and regulation of numerous physiological processes in health and disease. Naturally released from virtually all cells, these vesicles contain an array of nucleic acids, lipids and proteins which they transfer to target cells within their local milieu and systemically. They have been proposed as a means of "cell-free, cell therapy" for cancer, immune disorders, and more recently cardiovascular disease...
March 15, 2018: AAPS Journal
Dicson Sheeja Malar, Venkatesan Suryanarayanan, Mani Iyer Prasanth, Sanjeev Kumar Singh, Krishnaswamy Balamurugan, Kasi Pandima Devi
Amyloid beta (Aβ) formation is one of the neuropathological hallmarks of Alzheimer's disease (AD), which induces the generation of reactive oxygen species (ROS), further leading to the alteration of several signalling pathways. In the present study, vitexin has been evaluated for its neuroprotective activity against Aβ25-35 induced toxicity in Neuro-2a cells. Results of cell free studies indicated that vitexin significantly inhibited the aggregation of Aβ25-35 . Studies in Neuro-2a cells revealed that Aβ25-35 significantly affected the cell viability by inducing ROS mediated toxicity and apoptosis...
March 12, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
Sarah Caughlin, Shikhar Maheshwari, Yuksel Agca, Cansu Agca, Aaron J Harris, Kristina Jurcic, Ken K-C Yeung, David F Cechetto, Shawn N Whitehead
BACKGROUND: Accumulation of simple gangliosides GM2 and GM3, and gangliosides with longer long-chain bases (d20:1) have been linked to toxicity and the pathogenesis of Alzheimer's disease (AD). Conversely, complex gangliosides, such as GM1, have been shown to be neuroprotective. Recent evidence using matrix-assisted laser desorption ionization imaging mass spectrometry (MALDI-IMS) has demonstrated that a-series gangliosides are differentially altered during normal aging, yet it remains unclear how simple species are shifting relative to complex gangliosides in the prodromal stages of AD...
March 12, 2018: Biochimica et Biophysica Acta
Louise Wogelred, Fredrik Höök, Björn Agnarsson, Peter Sjövall
Accurate detection and quantification of individual molecules is important for the development of improved diagnostic methods as well as biochemical characterization of disease progression and treatments. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) is a surface analysis technique capable of imaging the distribution of specific molecules on surfaces with a high spatial resolution (<1 μm) and high sensitivity. ToF-SIMS is particularly suitable for detection of molecules up to ∼2 kDa, including lipids, whereas larger molecules, such as peptides and proteins, are fragmented during analysis, which makes them difficult to identify...
March 15, 2018: Biointerphases
Majid Vahed, Saburo Neya, Katsumi Matsuzaki, Tyuji Hoshino
The interaction of amyloid beta (Aβ) peptide with cell membrane is one of the factors enhancing Aβ aggregation, which is closely related to neuro-disturbance disease. In this work, we performed molecular dynamics (MD) simulation to investigate the initial stage of adhesion of Aβ40 to a GM1 ganglioside-containing membrane. Conformational change of Aβ40 due to interaction with the membrane was monitored and compared with that of Aβ42 observed in the previous study. Multiple computational trials were executed to analyze the probability of Aβ binding using a calculation model consisting of a GM1-containing mixed lipid membrane, water layer, ions, and Aβ40...
March 14, 2018: Journal of Physical Chemistry. B
Guillaume Sallé, Roz Laing, James A Cotton, Kirsty Maitland, Axel Martinelli, Nancy Holroyd, Alan Tracey, Matthew Berriman, W David Smith, George F J Newlands, Eve Hanks, Eileen Devaney, Collette Britton
Some nematode species are economically important parasites of livestock, while others are important human pathogens causing some of the most important neglected tropical diseases. In both humans and animals, anthelmintic drug administration is the main control strategy, but the emergence of drug-resistant worms has stimulated the development of alternative control approaches. Among these, vaccination is considered to be a sustainable and cost effective strategy. Currently, Barbervax® for the ruminant strongylid Haemonchus contortus is the only registered subunit vaccine for a nematode parasite, although a vaccine for the human hookworm Necator americanus is undergoing clinical trials (HOOKVAC consortium)...
March 10, 2018: International Journal for Parasitology
Vijayaraghavan Rangachari, Dexter N Dean, Pratip Rana, Ashwin Vaidya, Preetam Ghosh
Self-templating propagation of protein aggregate conformations is increasingly becoming a significant factor in many neurological diseases. In Alzheimer disease (AD), intrinsically disordered amyloid-β (Aβ) peptides undergo aggregation that is sensitive to environmental conditions. High-molecular weight aggregates of Aβ that form insoluble fibrils are deposited as senile plaques in AD brains. However, low-molecular weight aggregates called soluble oligomers are known to be the primary toxic agents responsible for neuronal dysfunction...
March 8, 2018: Biochimica et Biophysica Acta
Daniela Mendes, Maria Manuel Oliveira, Paula I Moreira, João Coutinho, Fernando M Nunes, David M Pereira, Patrícia Valentão, Paula B Andrade, Romeu A Videira
The development of effective medicines to break or delay the progressive brain degeneration underlying cognitive decline and dementia that characterize Alzheimer's disease (AD) is one of the greatest challenges of our time. In the present work, a selective pool of polyphenols, obtained from the white wine by adsorption to polyvinylpyrrolidone polymer (PVPP), was used to prepare a polyphenols-enriched diet, supplementing the drinking water with 100 mg/L (expressed as gallic acid equivalent) of wine polyphenolic extract...
February 10, 2018: Journal of Nutritional Biochemistry
Jennifer Rieusset
The contact sites that the endoplasmic reticulum (ER) forms with mitochondria, called mitochondria-associated membranes (MAMs), are a hot topic in biological research, and both their molecular determinants and their numerous roles in several signaling pathways are is continuously evolving. MAMs allow the exchange between both organelles of lipids, calcium (Ca2+ ), and likely reactive oxygen species, allowing adaptations of both cellular bioenergetics and cell fate depending of cellular needs or stresses. Therefore, it is not surprising that MAMs affect cellular metabolism...
March 9, 2018: Cell Death & Disease
Alanna Sedgwick, M Olivia Balmert, Crislyn D'Souza-Schorey
Aberrant cellular cholesterol accumulation contributes to the pathophysiology of many diseases including neurodegenerative disorders such as Niemann-Pick Type C (NPC) and Alzheimer's Disease1-4 . Many aspects of cholesterol efflux from cells remain elusive. Here we describe the utility of cholesterol-rich giant plasma membrane vesicles (GPMVs) as a means to monitor cholesterol that is translocated to the plasma membrane for secretion. We demonstrate that small molecules known to enhance lipid efflux, including those in clinical trials for lipid storage disorders, enhance this GPMV formation...
March 6, 2018: Experimental Cell Research
A R Ramirez, O L Acosta, M B Maya, M El-Hafidi
In metabolic diseases such as obesity, metabolic syndrome and type II diabetes, the over-expression of uncoupling proteins (UCPs) in a response to increased reactive oxygen species (ROS) generation by mitochondrial respiratory complexes, and to the excess of free fatty acid (FFA) supply from adipose tissue, may protect cells from oxidative stress, lipotoxicity and in turn from death. UCPs by reducing superoxide anion and H2O2 generation trigger several signals to cell for their adaptation to the lipotoxic microenvironment...
March 7, 2018: Current Molecular Medicine
Yong-Seok Kim, Jae-Sung Ahn, Semi Kim, Hyun-Jin Kim, Shin-Hee Kim, Ju-Seop Kang
Exosomes are membranous vesicles of 30-150 nm in diameter that are derived from the exocytosis of the intraluminal vesicles of many cell types including immune cells, stem cells, cardiovascular cells and tumor cells. Exosomes participate in intercellular communication by delivering their contents to recipient cells, with or without direct contact between cells, and thereby influence physiological and pathological processes. They are present in various body fluids and contain proteins, nucleic acids, lipids, and microRNAs that can be transported to surrounding cells...
March 2018: Korean Journal of Physiology & Pharmacology
Marco Busnelli, Stefano Manzini, Cinzia Parolini, Diana Escalante-Alcalde, Giulia Chiesa
LPP3 is an integral membrane protein belonging to a family of enzymes (LPPs) that display broad substrate specificity and catalyse dephosphorylation of several lipid substrates, including lysophosphatidic acid and sphingosine-1-phosphate. In mammals, the LPP family consists of three enzymes named LPP1, LPP2 and LPP3, which are encoded by three independent genes, PLPP1, PLPP2 and PLPP3, respectively (formerly known as PPAP2A, PPAP2C, PPAP2B). These three enzymes, in vitro, do not seem to differ for catalytic activities and substrate preferences...
March 2, 2018: Atherosclerosis
Joana Maia, Sergio Caja, Maria Carolina Strano Moraes, Nuno Couto, Bruno Costa-Silva
Tumors are not isolated entities, but complex systemic networks involving cell-cell communication between transformed and non-transformed cells. The milieu created by tumor-associated cells may either support or halt tumor progression. In addition to cell-cell contact, cells communicate through secreted factors via a highly complex system involving characteristics such as ligand concentration, receptor expression and integration of diverse signaling pathways. Of these, extracellular vesicles, such as exosomes, are emerging as novel cell-cell communication mediators in physiological and pathological scenarios...
2018: Frontiers in Cell and Developmental Biology
Ambadi Thody Sabareesan, M K Mathew, Jayant B Udgaonkar
The cellular prion protein (PrPC ), which is present ubiquitously in all mammalian neurons, is normally found to be linked to the cell membrane through a glycosylphosphatidylinositol (GPI) anchor. The conformational conversion of PrPC into misfolded and aggregated forms is associated with transmissible neurodegenerative diseases known as prion diseases. The importance of different misfolded conformations in prion diseases, and the mechanism by which prion aggregates induce neurotoxicity remain poorly understood...
March 4, 2018: Biochimica et Biophysica Acta
Benjamin Delprat, Tangui Maurice, Cécile Delettre
Wolfram syndrome (WS) is a rare neurodegenerative disease, the main pathological hallmarks of which associate with diabetes, optic atrophy, and deafness. Other symptoms may be identified in some but not all patients. Prognosis is poor, with death occurring around 35 years of age. To date, no treatment is available. WS was first described as a mitochondriopathy. However, the localization of the protein on the endoplasmic reticulum (ER) membrane challenged this hypothesis. ER contacts mitochondria to ensure effective Ca2+ transfer, lipids transfer, and apoptosis within stabilized and functionalized microdomains, termed "mitochondria-associated ER membranes" (MAMs)...
March 6, 2018: Cell Death & Disease
Bengang Xing, Xiangzhao Ai, Ming Hu, Zhimin Wang, Wenmin Zhang, Juan Li, Jun Lin, Huang-Hao Yang
In terms of the extremely small size and large specific surface area, nanomaterials often exhibit unusual physical and chemical properties, which have recently attracted considerable attention in bionanotechnology and nanomedicine. Currently, the extensive usage of nanotechnology in medicine holds the great potential for precise diagnosis and effective therapeutics of various human diseases in clinical practice in past decades. However, a detailed understanding regarding how nanomedicines interact with the intricate environment in complex living systems remains a pressing and challenging goal...
March 6, 2018: Bioconjugate Chemistry
Zhen-Yu Yao, Wen-Bin Chen, Shan-Shan Shao, Shi-Zhan Ma, Chong-Bo Yang, Meng-Zhu Li, Jia-Jun Zhao, Ling Gao
Metabolic disorders are classified clinically as a complex and varied group of diseases including metabolic syndrome, obesity, and diabetes mellitus. Fat toxicity, chronic inflammation, and oxidative stress, which may change cellular functions, are considered to play an essential role in the pathogenetic progress of metabolic disorders. Recent studies have found that cells secrete nanoscale vesicles containing proteins, lipids, nucleic acids, and membrane receptors, which mediate signal transduction and material transport to neighboring and distant cells...
2018: Journal of Zhejiang University. Science. B
Efrem N Tessema, Tsige Gebre-Mariam, Getahun Paulos, Johannes Wohlrab, Reinhard H H Neubert
Deficiency or altered composition of stratum corneum (SC) lipids such as ceramides (CERs), causing skin barrier dysfunction and skin dryness, have been associated with skin diseases such as atopic dermatitis and psoriasis, and ageing. Replenishing the depleted native CERs with exogenous CERs has also been shown to have beneficial effects in restoring the skin barrier. Phyto-derived CERs such as oat CERs were shown to be potential for skin barrier reinforcement. To effect this, however, the oat CERs should overcome the SC barrier and delivered deep into the lipid matrix using the various novel formulations...
February 28, 2018: European Journal of Pharmaceutics and Biopharmaceutics
Guoyuan Qi, Rui Guo, Haoyu Tian, Lixia Li, Hua Liu, Yashi Mi, Xuebo Liu
SCOPE: Circadian clock plays a principal role in orchestrating our daily physiology and metabolism, and their perturbation can evoke metabolic diseases such as fatty liver and insulin resistance. Nobiletin (NOB) has been demonstrated to possess antitumor and neuroprotective activities. The objective of the current study is to determine potential effects of NOB on modulating the core clock gene Bmal1 regarding ameliorating glucolipid metabolic disorders. RESULTS: Our results revealed that NOB partially reverse the relatively shallow daily oscillations of circadian clock genes and reset phase-shifting circadian rhythms in primary hepatocytes under metabolic disorders conditions...
February 28, 2018: Biochimica et Biophysica Acta
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