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Neurodegenerative disease

Raquel Marin, Noemí Fabelo, Virginia Martín, Paula Garcia-Esparcia, Isidre Ferrer, David Quinto-Alemany, Mario Díaz
Lipid rafts are highly dynamic membrane microdomains intimately associated with cell signaling. Compelling evidence has demonstrated that alterations in lipid rafts are associated with neurodegenerative diseases such Alzheimer's disease, but at present, whether alterations in lipid raft microdomains occur in other types of dementia such dementia with Lewy bodies (DLB) remains unknown. Our analyses reveal that lipid rafts from DLB exhibit aberrant lipid profiles including low levels of n-3 long-chain polyunsaturated fatty acids (mainly docosahexaenoic acid), plasmalogens and cholesterol, and reduced unsaturation and peroxidability indexes...
September 6, 2016: Neurobiology of Aging
Allegra T Aron, Morten O Loehr, Jana Bogena, Christopher J Chang
Iron is essential for sustaining life, as its ability to cycle between multiple oxidation states is critical for catalyzing chemical transformations in biological systems. However, without proper regulation, this same redox capacity can trigger oxidative stress events that contribute to aging along with diseases ranging from cancer to cardiovascular and neurodegenerative disorders. Despite its importance, methods for monitoring biological iron bound weakly to cellular ligands-the labile iron pool-to generate a response that preserves spatial and temporal information remain limited, owing to the potent fluorescence quenching ability of iron...
October 21, 2016: Journal of the American Chemical Society
Marion T Turnbull, Elizabeth J Coulson
Alzheimer's disease (AD) is a progressive, irreversible neurodegenerative disease that destroys memory and cognitive function. Aggregates of hyperphosphorylated tau protein are a prominent feature in the brain of patients with AD, and are a major contributor to neuronal toxicity and disease progression. However, the factors that initiate the toxic cascade that results in tau hyperphosphorylation in sporadic AD are unknown. Here we investigated whether degeneration of basal forebrain cholinergic neurons (BFCNs) and/or a resultant decrease in neurotrophin signaling cause aberrant tau hyperphosphorylation...
October 20, 2016: Journal of Alzheimer's Disease: JAD
Maria Anderson, Feng Xu, Ming-Hsuan Ou-Yang, Judianne Davis, William E Van Nostrand, John K Robinson
Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is the leading cause of dementia in the elderly. Amyloid-β protein (Aβ) depositions in both the brain parenchyma and the cerebral vasculature are recognized as important pathological components that contribute to the cognitive impairments found in individuals with AD. Because pharmacological options have been minimally effective in treating cognitive impairment to date, interest in the development of preventative lifestyle intervention strategies has increased in the field...
October 19, 2016: Journal of Alzheimer's Disease: JAD
Tanja Macheiner, Vera Heike Ingeborg Fengler, Marlene Agreiter, Tobias Eisenberg, Frank Madeo, Dagmar Kolb, Berthold Huppertz, Richard Ackbar, Karine Sargsyan
In the course of mitochondrial diseases standard care mostly focuses on treatment of symptoms, while therapeutic approaches aimed at restoring mitochondrial function are currently still in development. The transfer of healthy or modified mitochondria into host cells would open up the possibilities of new cell therapies. Therefore, in this study, a novel method of mitochondrial transfer is proposed by anti-TOM22 magnetic bead-labeled mitochondria with the assistance of a magnetic plate. In comparison to the passive transfer method, the magnetomitotransfer method was more efficient at transferring mitochondria into cells (78-92% vs 0-17% over 3 days)...
October 21, 2016: Scientific Reports
Przemyslaw Jurczak, Patrick Groves, Aneta Szymanska, Sylwia Rodziewicz-Motowidlo
Human cystatin C (hCC) is a small protein belonging to the cystatin family of papain-like cysteine proteinase inhibitors. We review the recent literature concerning structural aspects of hCC related to disease. We focus on the mechanisms of hCC dimerization, oligomerization and amyloid formation. Amyloid formation is associated with a number of neurodegenerative diseases that affect the independence and quality of life of aging populations. hCC is one of the second wave proteins that have been found to undergo amyloidosis associated with disease...
October 19, 2016: FEBS Letters
Mercedes Garcia-Gil, Elisabetta Albi
In the last 20 years it has been widely demonstrated that cell nucleus contains neutral and polar lipids localized in nuclear membranes, nucleoli, nuclear matrix and chromatin. Nuclear lipids may show specific organization forming nuclear lipid microdomains and have both structural and functional roles. Depending on their localization, nuclear lipids play different roles such as the regulation of nuclear membrane and nuclear matrix fluidity but they also can act as platforms for vitamin and hormone function, for active chromatin anchoring, and for the regulation of gene expression, DNA duplication and transcription...
October 20, 2016: Neurochemical Research
Dah Ihm Kim, Ki Hoon Lee, Ji Young Oh, Jun Sung Kim, Ho Jae Han
Mitochondria as dynamic organelles undergo morphological changes through the processes of fission and fusion which are major factors regulating their functions. A disruption in the balance of mitochondrial dynamics induces functional disorders in mitochondria such as failed energy production and the generation of reactive oxygen species, which are closely related to pathophysiological changes associated with Alzheimer's disease (AD). Recent studies have demonstrated a relationship between abnormalities in mitochondrial dynamics and impaired mitochondrial function, clarifying the effects of morphofunctional aberrations which promote neuronal cell death in AD...
October 20, 2016: Cellular and Molecular Neurobiology
Young Joon Kwon, Marni J Falk, Michael J Bennett
CLN3 disease (Spielmeyer-Vogt-Sjogren-Batten disease, previously known as classic juvenile neuronal ceroid lipofuscinosis, NCL) is a pediatric-onset progressive neurodegenerative disease characterized by progressive vision loss, seizures, loss of cognitive and motor function, and early death. While no precise biochemical mechanism or therapies are known, the pathogenesis of CLN3 disease involves intracellular calcium accumulation that may trigger apoptosis. Our prior work in in vitro cell models of CLN3 deficiency suggested that FDA-approved calcium channel antagonists may have therapeutic value...
October 20, 2016: Journal of Inherited Metabolic Disease
Ewa Papuć, Konrad Rejdak
There is emerging evidence that glial cells are involved in the neuropathological process in Parkinson's disease (PD) in addition to degeneration of neuronal structures. Recently, we confirmed the presence of an adaptive immune response against different glial-derived antigens in PD, with a possible role of anti-MAG, anti-MBP and anti-PLP antibodies in the disease progression. The aim of the present study was to assess humoral response against myelin-associated glycoprotein (MAG) in patients with parkinsonism (both idiopathic and atypical) to check whether these antibodies could serve as biomarkers of PD, its severity and progression...
October 20, 2016: Journal of Neural Transmission
Kosuke Kawaguchi, Masashi Morita
ATP-binding cassette (ABC) transporters are one of the largest families of membrane-bound proteins and transport a wide variety of substrates across both extra- and intracellular membranes. They play a critical role in maintaining cellular homeostasis. To date, four ABC transporters belonging to subfamily D have been identified. ABCD1-3 and ABCD4 are localized to peroxisomes and lysosomes, respectively. ABCD1 and ABCD2 are involved in the transport of long and very long chain fatty acids (VLCFA) or their CoA-derivatives into peroxisomes with different substrate specificities, while ABCD3 is involved in the transport of branched chain acyl-CoA into peroxisomes...
2016: BioMed Research International
David Fällmar, Johan Lilja, Lena Kilander, Torsten Danfors, Mark Lubberink, Elna-Marie Larsson, Jens Sörensen
The dosage of (18)F-FDG must be sufficient to ensure adequate PET image quality. For younger patients and research controls, the lowest possible radiation dose should be used. The purpose of this study was to find a protocol for FDG-PET of the brain with reduced radiation dose and preserved quantitative characteristics. Eight patients with neurodegenerative disorders and nine controls (n=17) underwent FDG-PET/CT twice on separate occasions, first with normal-dose (3 MBq/kg), and second with low-dose (0.75 MBq/kg, 25% of the original)...
2016: American Journal of Nuclear Medicine and Molecular Imaging
Alba Di Pardo, Enrico Amico, Vittorio Maglione
Huntington Disease (HD) is a genetic neurodegenerative disorder characterized by broad types of cellular and molecular dysfunctions that may affect both neuronal and non-neuronal cell populations. Among all the molecular mechanisms underlying the complex pathogenesis of the disease, alteration of sphingolipids has been identified as one of the most important determinants in the last years. In the present study, besides the purpose of further confirming the evidence of perturbed metabolism of gangliosides GM1, GD1a, and GT1b the most abundant cerebral glycosphingolipids, in the striatal and cortical tissues of HD transgenic mice, we aimed to test the hypothesis that abnormal levels of these lipids may be found also in the corpus callosum white matter, a ganglioside-enriched brain region described being dysfunctional early in the disease...
2016: Frontiers in Neuroscience
Andreas Hahn, Martin Schain, Maria Erlandsson, Petter Sjölin, Gregory M James, Olof T Strandberg, Douglas Hägerström, Rupert Lanzenberger, Jonas Jögi, Tomas G Olsson, Ruben Smith, Oskar Hansson
: Aggregation of hyperphosphorylated tau is a major hallmark of many neurodegenerative diseases, including Alzheimer's disease. In vivo imaging with positron emission tomography (PET) may offer important insights in pathophysiological mechanisms, diagnosis and disease progression. We describe different strategies for quantification of (18)F-AV1451 (T807) tau binding, including models with blood sampling and non-invasive alternatives. METHODS: 15 subjects (4 controls, 6 Alzheimer's disease (AD), 3 progressive supranuclear palsy (PSP), 2 cortico basal syndrome (CBS)) underwent 180 min PET with (18)F-AV1451 and arterial blood sampling...
October 20, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
E H Baker, S W Levin, Z Zhang, A B Mukherjee
BACKGROUND AND PURPOSE: Infantile neuronal ceroid lipofuscinosis is a devastating neurodegenerative storage disease caused by palmitoyl-protein thioesterase 1 deficiency, which impairs degradation of palmitoylated proteins (constituents of ceroid) by lysosomal hydrolases. Consequent lysosomal ceroid accumulation leads to neuronal injury, resulting in rapid neurodegeneration and childhood death. As part of a project studying the treatment benefits of a combination of cysteamine bitartrate and N-acetyl cysteine, we made serial measurements of patients' brain volumes with MR imaging...
October 20, 2016: AJNR. American Journal of Neuroradiology
Maria I Ventura, Deborah E Barnes, Jessica M Ross, Kimberly E Lanni, Karen A Sigvardt, Elizabeth A Disbrow
Parkinson's disease (PD) is a progressive neurodegenerative disease associated with deficits in motor, cognitive, and emotion/quality of life (QOL) domains, yet most pharmacologic and behavioral interventions focus only on motor function. Our goal was to perform a pilot study of Dance for Parkinson's-a community-based program that is growing in popularity-in order to compare effect sizes across multiple outcomes and to inform selection of primary and secondary outcomes for a larger trial. Study participants were people with PD who self-enrolled in either Dance for Parkinson's classes (intervention group, N=8) or PD support groups (control group, N=7)...
October 17, 2016: Contemporary Clinical Trials
Giorgio Biasiotto, Silvana Archetti, Diego Di Lorenzo, Francesca Merola, Giulia Paiardi, Barbara Borroni, Antonella Alberici, Alessandro Padovani, Massimiliano Filosto, Cristian Bonvicini, Luigi Caimi, Isabella Zanella
Although large expansions of the non-coding GGGGCC repeat in C9orf72 gene are clearly defined as pathogenic for Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Lobar Degeneration (FTLD), intermediate-length expansions have also been associated with those and other neurodegenerative diseases. Intermediate-length allele sizing is complicated by intrinsic properties of current PCR-based methodologies, in that somatic mosaicism could be suspected. We designed a protocol that allows the exact sizing of intermediate-length alleles, as well as the identification of large expansions...
October 17, 2016: Molecular and Cellular Probes
Shearwood McClelland, Joseph F Baker, Justin S Smith, Breton G Line, Thomas J Errico, Christopher P Ames, R Shay Bess
Parkinson's disease (PD) is a neurodegenerative disorder manifesting over time to result in reduced mobility. The impact of PD on spinal fusion has yet to be addressed on a nationwide level. The Nationwide Inpatient Sample (NIS) from 2001 to 2012 was used for analysis. Admissions with spinal fusion of two or more vertebrae (ICD-9 codes=81.62, 81.63 and 81.64) were included and then stratified based on the presence or absence of PD (ICD-9 code=332.0); patients with cancer (ICD-9 codes=140-239) or trauma (ICD-9 codes=805...
October 17, 2016: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
Hyeon-Joong Kim, Dae-Joong Kim, Eun-Ju Shin, Byung-Hwan Lee, Sun-Hye Choi, Sung-Hee Hwang, Hyewhon Rhim, Ik-Hyun Cho, Hyoung-Chun Kim, Seung-Yeol Nah
We previously showed that gintonin, an exogenous lysophosphatidic acid (LPA) receptor ligand, attenuated β-amyloid plaque formation in the cortex and hippocampus, and restored β-amyloid-induced memory dysfunction. Both endogenous LPA and LPA receptors play a key role in embryonic brain development. However, little is known about whether gintonin can induce hippocampal cell proliferation in adult wild-type mice and an APPswe/PSEN-1 double Tg mouse model of Alzheimer's disease (AD). In the present study, we examined the effects of gintonin on the proliferation of hippocampal neural progenitor cells (NPCs) in vitro and its effects on the hippocampal cell proliferation in wild-type mice and a transgenic AD mouse model...
October 17, 2016: Neurochemistry International
Ruijie Zhang, Nana Zhang, Hai Zhang, Chunxiao Liu, Xiaoqing Dong, Xiaoxue Wang, Yu Zhu, Chong Xu, Lei Liu, Sijun Yang, Shile Huang, Long Chen
BACKGROUND AND PURPOSE: Increasing evidence has suggested cadmium (Cd), as an inducer of reactive oxygen species (ROS), is a potential pathogenic factor in human neurodegenerative diseases. Thus, it is important to find effective interventions for Cd-induced oxidative stress in the central nervous system. The purpose of this study was to determine whether and how celastrol, a plant-derived triterpene, could mitigate Cd-induced ROS and cell death in neuronal cells. EXPERIMENTAL APPROACH: PC12, SH-SY5Y cells and primary murine neurons were chosen as a model to study celastrol neuroprotection against Cd-poisoning...
October 20, 2016: British Journal of Pharmacology
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