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https://www.readbyqxmd.com/read/28213071/pla2g6-accumulates-in-lewy-bodies-in-park14-and-idiopathic-parkinson-s-disease
#1
Yasuo Miki, Kunikazu Tanji, Fumiaki Mori, Akiyoshi Kakita, Hitoshi Takahashi, Koichi Wakabayashi
The histopathological hallmark of Parkinson's disease (PD) and dementia with Lewy bodies (DLB) is the occurrence of insoluble fibrillary aggregates known as Lewy bodies, in which phosphorylated α-synuclein (α-syn) is a major component. To date, familial PD-linked gene products, including α-syn, parkin, PINK-1, DJ-1 and LRRK2, are known to be involved in Lewy body formation. Phospholipase A2, group VI (PLA2G6) is the causative gene for PARK14-linked parkinsonism (PARK14), a familial form of juvenile-onset dystonia parkinsonism...
February 14, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28203202/plasma-exosomes-spread-and-cluster-around-%C3%AE-amyloid-plaques-in-an-animal-model-of-alzheimer-s-disease
#2
Tingting Zheng, Jiali Pu, Yanxing Chen, Yanfang Mao, Zhangyu Guo, Hongyu Pan, Ling Zhang, Heng Zhang, Binggui Sun, Baorong Zhang
Exosomes, a type of extracellular vesicle, have been shown to be involved in many disorders, including Alzheimer's disease (AD). Exosomes may contribute to the spread of misfolded proteins such as amyloid-β (Aβ) and α-synuclein. However, the specific diffusion process of exosomes and their final destination in brain are still unclear. In the present study, we isolated exosomes from peripheral plasma and injected them into the hippocampus of an AD mouse model, and investigated exosome diffusion. We found that injected exosomes can spread from the dentate gyrus (DG) to other regions of hippocampus and to the cortex...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28190674/neuronal-loss-and-%C3%AE-synuclein-pathology-in-the-superior-colliculus-and-its-relationship-to-visual-hallucinations-in-dementia-with-lewy-bodies
#3
Daniel Erskine, Alan J Thomas, John-Paul Taylor, Michael A Savage, Johannes Attems, Ian G McKeith, Christopher M Morris, Ahmad A Khundakar
OBJECTIVE: Patients with dementia with Lewy bodies (DLB) often experience visual hallucinations, which are related to decreased quality of life for patients and increased caregiver distress. The pathologic changes that contribute to visual hallucinations are not known, but several hypotheses implicate deficient attentional processing. The superior colliculus has a role in visual attention and planning eye movements and has been directly implicated in several models of visual hallucinations...
January 10, 2017: American Journal of Geriatric Psychiatry
https://www.readbyqxmd.com/read/28180219/super-resolution-imaging-of-alpha-synuclein-polymorphisms-and-their-potential-role-in-neurodegeneration
#4
REVIEW
Eileen Nugent, Clemens F Kaminski, Gabriele S Kaminski Schierle
The conversion of soluble, functional proteins into amyloid fibrils has been linked to the development of neurodegenerative disorders, including Parkinson's and Alzheimer's disease. In the brains of patients with these disorders, the increasing presence of amyloid-containing plaques corresponds to neuronal cell death and the worsening of symptoms. However, protein amyloids are not merely confined to dying cells. Rather, some show a propensity to be transmitted to, and enter adjacent cells and induce the polymerization of the native monomer population...
February 9, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/28170377/%C3%AE-synuclein-toxicity-in-neurodegeneration-mechanism-and-therapeutic-strategies
#5
REVIEW
Yvette C Wong, Dimitri Krainc
Alterations in α-synuclein dosage lead to familial Parkinson's disease (PD), and its accumulation results in synucleinopathies that include PD, dementia with Lewy bodies (DLB) and multiple system atrophy (MSA). Furthermore, α-synuclein contributes to the fibrilization of amyloid-b and tau, two key proteins in Alzheimer's disease, which suggests a central role for α-synuclein toxicity in neurodegeneration. Recent studies of factors contributing to α-synuclein toxicity and its disruption of downstream cellular pathways have expanded our understanding of disease pathogenesis in synucleinopathies...
February 7, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28160067/tau-aggregation-influences-cognition-and-hippocampal-atrophy-in-the-absence-of-beta-amyloid-a-clinico-imaging-pathological-study-of-primary-age-related-tauopathy-part
#6
Keith A Josephs, Melissa E Murray, Nirubol Tosakulwong, Jennifer L Whitwell, David S Knopman, Mary M Machulda, Stephen D Weigand, Bradley F Boeve, Kejal Kantarci, Leonard Petrucelli, Val J Lowe, Clifford R Jack, Ronald C Petersen, Joseph E Parisi, Dennis W Dickson
We investigate whether there is any association between the Braak neurofibrillary tangle (NFT) stage and clinical and MRI features in definite primary age-related tauopathy (PART). We analysed 52 cases with a Braak NFT tangle stage >0 and ≤IV, and a Thal phase of 0 (no beta-amyloid present). Twenty-nine (56%) were female. Median age at death was 88 years (IQR 82-92 years). Fifteen (29%) were TDP-positive (75% TDP stage I), 16 (31%) had argyrophilic grain disease and three (6%) had alpha-synuclein-positive Lewy bodies...
February 3, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28159621/potential-biomarkers-and-novel-pharmacological-targets-in-protein-aggregation-related-neurodegenerative-diseases
#7
REVIEW
Chiara Giacomelli, Simona Daniele, Claudia Martini
The aggregation of specific proteins plays a pivotal role in the etiopathogenesis of several neurodegenerative diseases (NDs). β-Amyloid (Aβ) peptide-containing plaques and intraneuronal neurofibrillary tangles composed of hyperphosphorylated protein tau are the two main neuropathological lesions in Alzheimer's disease. Meanwhile, Parkinson's disease is defined by the presence of intraneuronal inclusions (Lewy bodies), in which α-synuclein (α-syn) has been identified as a major protein component. The current literature provides considerable insights into the mechanisms underlying oligomeric-related neurodegeneration, as well as the relationship between protein aggregation and ND, thus facilitating the development of novel putative biomarkers and/or pharmacological targets...
January 31, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28154522/metal-dyshomeostasis-and-their-pathological-role-in-prion-and-prion-like-diseases-the-basis-for-a-nutritional-approach
#8
REVIEW
Mattia Toni, Maria L Massimino, Agnese De Mario, Elisa Angiulli, Enzo Spisni
Metal ions are key elements in organisms' life acting like cofactors of many enzymes but they can also be potentially dangerous for the cell participating in redox reactions that lead to the formation of reactive oxygen species (ROS). Any factor inducing or limiting a metal dyshomeostasis, ROS production and cell injury may contribute to the onset of neurodegenerative diseases or play a neuroprotective action. Transmissible spongiform encephalopathies (TSEs), also known as prion diseases, are a group of fatal neurodegenerative disorders affecting the central nervous system (CNS) of human and other mammalian species...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28132929/identification-of-brain-substrates-of-transglutaminase-by-functional-proteomics-supports-its-role-in-neurodegenerative-diseases
#9
William André, Isabelle Nondier, Maud Valensi, François Guillonneau, Christian Federici, Guylaine Hoffner, Philippe Djian
Transglutaminases are calcium-dependent enzymes that catalyze the formation of ε-(γ-glutamyl)lysine isopeptide bonds between specific glutamine and lysine residues. Some transglutaminase isoforms are present in the brain and are thought to participate in the protein aggregation characteristic of neurological diseases such as Huntington, Alzheimer's and Parkinson's disease. We have developed a functional proteomics strategy in which biotinylated amine-donor and amine-acceptor probes were used to identify the transglutaminase substrates present in brain...
January 26, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28108532/tdp-43-prions
#10
Takashi Nonaka, Masato Hasegawa
The most common neurodegenerative diseases, such as Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis, are all protein-misfolding diseases and are characterized by the presence of disease-specific protein aggregates in affected neuronal cells. Recent studies have shown that, like tau and α-synuclein, TAR-DNA binding protein of 43 kDa (TDP-43) can form aggregates in vitro in a seed-dependent, self-templating, prion-like manner. Insoluble TDP-43 prepared from the brains of patients has been classified into several strains, which can be transferred from cell to cell in vitro, suggesting the involvement of mechanisms reminiscent of those by which prions spread through the nervous system...
January 20, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28071698/increased-levels-of-csf-total-but-not-oligomeric-or-phosphorylated-forms-of-alpha-synuclein-in-patients-diagnosed-with-probable-alzheimer-s-disease
#11
Nour K Majbour, Davide Chiasserini, Nishant N Vaikath, Paolo Eusebi, Takahiko Tokuda, Wilma van de Berg, Lucilla Parnetti, Paolo Calabresi, Omar M A El-Agnaf
Several studies reported an association between CSF alpha-synuclein (α-syn) and tau in Alzheimer's disease (AD), and demonstrated the significance of α-syn in improving the diagnostic sensitivity/specificity of classical AD CSF biomarkers. In the current study, we measured CSF levels of different α-syn species in a cohort of AD patients (n = 225) who showed a CSF profile typical of AD at baseline as well as in cognitively intact controls (n = 68). CSF total α-syn (t-α-syn) significantly increased in the AD group (p < 0...
January 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28056734/metal-nanoparticles-for-the-treatment-and-diagnosis-of-neurodegenerative-brain-diseases
#12
Valentina Vio, María José Marchant, Eyleen Araya, Marcelo J Kogan
This review focuses on the application of metal nanoparticles in the diagnosis and treatment of Alzheimer's and Parkinson's diseases. Metal nanoparticles present interesting physicochemical properties that can be applied to increase biomarker detection sensitivities in vitro and in vivo. Furthermore, these nanoparticles could be used in different strategies for the treatment of central nervous system diseases, particularly in regards to drug delivery. Herein, specific potential applications of metal nanoparticles are separately discussed for the contexts of in vitro diagnoses and treatments...
January 5, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28050792/alpha-synuclein-alters-differently-gene-expression-of-sirts-parps-and-other-stress-response-proteins-implications-for-neurodegenerative-disorders
#13
J Motyl, P L Wencel, M Cieślik, R P Strosznajder, J B Strosznajder
Alpha-synuclein (ASN) is a presynaptic protein that can easily change its conformation under different types of stress. It's assumed that ASN plays an important role in the pathogenesis of Parkinson's and Alzheimer's disease. However, the molecular mechanism of ASN toxicity has not been elucidated. This study focused on the role of extracellular ASN (eASN) in regulation of transcription of sirtuins (Sirts) and DNA-bound poly(ADP-ribose) polymerases (PARPs) - proteins crucial for cells' survival/death. Our results indicate that eASN enhanced the free radicals level, decreased mitochondria membrane potential, cells viability and activated cells' death...
January 3, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28039370/hippocampal-%C3%AE-synuclein-in-dementia-with-lewy-bodies-contributes-to-memory-impairment-and-is-consistent-with-spread-of-pathology
#14
David H Adamowicz, Subhojit Roy, David P Salmon, Douglas R Galasko, Lawrence A Hansen, Eliezer Masliah, Fred H Gage
: Despite considerable research to uncover them, the anatomic and neuropathologic correlates of memory impairment in dementia with Lewy bodies (DLB) remain unclear. While some studies have implicated Lewy bodies in the neocortex, others have pointed to α-synuclein pathology in the hippocampus. We systematically examined hippocampal Lewy pathology and its distribution in hippocampal subfields in 95 clinically and neuropathologically characterized human cases of DLB, finding that α-synuclein pathology was highest in two hippocampal-related subregions: the CA2 subfield and the entorhinal cortex (EC)...
December 30, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27979356/neuropathological-and-genetic-correlates-of-survival-and-dementia-onset-in-synucleinopathies-a-retrospective-analysis
#15
David J Irwin, Murray Grossman, Daniel Weintraub, Howard I Hurtig, John E Duda, Sharon X Xie, Edward B Lee, Vivianna M Van Deerlin, Oscar L Lopez, Julia K Kofler, Peter T Nelson, Gregory A Jicha, Randy Woltjer, Joseph F Quinn, Jeffery Kaye, James B Leverenz, Debby Tsuang, Katelan Longfellow, Dora Yearout, Walter Kukull, C Dirk Keene, Thomas J Montine, Cyrus P Zabetian, John Q Trojanowski
BACKGROUND: Great heterogeneity exists in survival and the interval between onset of motor symptoms and dementia symptoms across synucleinopathies. We aimed to identify genetic and pathological markers that have the strongest association with these features of clinical heterogeneity in synucleinopathies. METHODS: In this retrospective study, we examined symptom onset, and genetic and neuropathological data from a cohort of patients with Lewy body disorders with autopsy-confirmed α synucleinopathy (as of Oct 1, 2015) who were previously included in other studies from five academic institutions in five cities in the USA...
January 2017: Lancet Neurology
https://www.readbyqxmd.com/read/27973581/the-role-of-dna-methylation-and-histone-modifications-in-neurodegenerative-diseases-a-systematic-review
#16
Ke-Xin Wen, Jelena Miliç, Bassem El-Khodor, Klodian Dhana, Jana Nano, Tammy Pulido, Bledar Kraja, Asija Zaciragic, Wichor M Bramer, John Troup, Rajiv Chowdhury, M Arfam Ikram, Abbas Dehghan, Taulant Muka, Oscar H Franco
IMPORTANCE: Epigenetic modifications of the genome, such as DNA methylation and histone modifications, have been reported to play a role in neurodegenerative diseases (ND) such as Alzheimer's disease (AD) and Parkinson's disease (PD). OBJECTIVE: To systematically review studies investigating epigenetic marks in AD or PD. METHODS: Eleven bibliographic databases (Embase.com, Medline (Ovid), Web-of-Science, Scopus, PubMed, Cinahl (EBSCOhost), Cochrane Central, ProQuest, Lilacs, Scielo and Google Scholar) were searched until July 11th 2016 to identify relevant articles...
2016: PloS One
https://www.readbyqxmd.com/read/27956640/loss-of-o-glcnac-glycosylation-in-forebrain-excitatory-neurons-induces-neurodegeneration
#17
Andrew C Wang, Elizabeth H Jensen, Jessica E Rexach, Harry V Vinters, Linda C Hsieh-Wilson
O-GlcNAc glycosylation (or O-GlcNAcylation) is a dynamic, inducible posttranslational modification found on proteins associated with neurodegenerative diseases such as α-synuclein, amyloid precursor protein, and tau. Deletion of the O-GlcNAc transferase (ogt) gene responsible for the modification causes early postnatal lethality in mice, complicating efforts to study O-GlcNAcylation in mature neurons and to understand its roles in disease. Here, we report that forebrain-specific loss of OGT in adult mice leads to progressive neurodegeneration, including widespread neuronal cell death, neuroinflammation, increased production of hyperphosphorylated tau and amyloidogenic Aβ-peptides, and memory deficits...
December 27, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27938414/the-effects-of-the-novel-a53e-alpha-synuclein-mutation-on-its-oligomerization-and-aggregation
#18
Diana F Lázaro, Mariana Castro Dias, Anita Carija, Susanna Navarro, Carolina Silva Madaleno, Sandra Tenreiro, Salvador Ventura, Tiago F Outeiro
α-synuclein (aSyn) is associated with both sporadic and familial forms of Parkinson's disease (PD), the second most common neurodegenerative disorder after Alzheimer's disease. In particular, multiplications and point mutations in the gene encoding for aSyn cause familial forms of PD. Moreover, the accumulation of aSyn in Lewy Bodies and Lewy neurites in disorders such as PD, dementia with Lewy bodies, or multiple system atrophy, suggests aSyn misfolding and aggregation plays an important role in these disorders, collectively known as synucleinopathies...
December 9, 2016: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/27934063/uncovering-the-binding-and-specificity-of-%C3%AE-wrapins-for-amyloid-%C3%AE-and-%C3%AE-synuclein
#19
Asuka A Orr, Michael M Wördehoff, Wolfgang Hoyer, Phanourios Tamamis
Amyloidogenic proteins amyloid-β peptide (Aβ) and α-synuclein (α-syn) self-assemble into fibrillar amyloid deposits, senile plaques and Lewy bodies, pathological features of Alzheimer's and Parkinson's diseases, respectively. Interestingly, a portion of Alzheimer's disease cases also exhibit aggregation of α-syn into Lewy bodies, and growing evidence also suggests that Aβ and α-syn oligomers are toxic. Therefore, the simultaneous inhibition through sequestration of the two amyloidogenic proteins may constitute a promising therapeutic strategy...
December 22, 2016: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/27919712/extracts-from-two-ubiquitous-mediterranean-plants-ameliorate-cellular-and-animal-models-of-neurodegenerative-proteinopathies
#20
Michelle Briffa, Stephanie Ghio, Johanna Neuner, Alison J Gauci, Rebecca Cacciottolo, Christelle Marchal, Mario Caruana, Christophe Cullin, Neville Vassallo, Ruben J Cauchi
A signature feature of age-related neurodegenerative proteinopathies is the misfolding and aggregation of proteins, typically amyloid-β (Aβ) in Alzheimer's disease (AD) and α-synuclein (α-syn) in Parkinson's disease (PD), into soluble oligomeric structures that are highly neurotoxic. Cellular and animal models that faithfully replicate the hallmark features of these disorders are being increasing exploited to identify disease-modifying compounds. Natural compounds have been identified as a useful source of bioactive molecules with promising neuroprotective capabilities...
December 2, 2016: Neuroscience Letters
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