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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
https://www.readbyqxmd.com/read/27918765/development-of-a-biochemical-diagnosis-of-parkinson-disease-by-detection-of-%C3%AE-synuclein-misfolded-aggregates-in-cerebrospinal-fluid
#11
Mohammad Shahnawaz, Takahiko Tokuda, Masaaki Waragai, Nicolas Mendez, Ryotaro Ishii, Claudia Trenkwalder, Brit Mollenhauer, Claudio Soto
Importance: Parkinson disease (PD) is a highly prevalent and incurable neurodegenerative disease associated with the accumulation of misfolded α-synuclein (αSyn) aggregates. An important problem in this disease is the lack of a sensitive, specific, and noninvasive biochemical diagnosis to help in clinical evaluation, monitoring of disease progression, and early differential diagnosis from related neurodegenerative diseases. Objective: To develop a novel assay with high sensitivity and specificity to detect small quantities of αSyn aggregates circulating in cerebrospinal fluid (CSF) of patients affected by PD and related synucleinopathies...
December 5, 2016: JAMA Neurology
https://www.readbyqxmd.com/read/27916654/prion-like-mechanisms-and-potential-therapeutic-targets-in-neurodegenerative-disorders
#12
REVIEW
Masato Hasegawa, Takashi Nonaka, Masami Masuda-Suzukake
Prion-like propagation of abnormal intracytoplasmic proteins, which are the defining features of major neurodegenerative disorders, such as Alzheimer's disease (AD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS), has been proposed. A growing body of evidence strongly suggests that abnormal tau, α-synuclein and TDP-43 have prion-like properties, convert the corresponding normal proteins into abnormal forms, and are transmitted from cell to cell, spreading throughout the brain. This idea is extremely important not only for understanding the pathogenesis and progression of these diseases, but also for the development of molecular therapies...
December 1, 2016: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27911312/increased-transforming-growth-factor-%C3%AE-2-in-the-neocortex-of-alzheimer-s-disease-and-dementia-with-lewy-bodies-is%C3%A2-correlated-with-disease-severity-and%C3%A2-soluble-a%C3%AE-42-load
#13
Joyce R Chong, Yuek Ling Chai, Jasinda H Lee, David Howlett, Johannes Attems, Clive G Ballard, Dag Aarsland, Paul T Francis, Christopher P Chen, Mitchell K P Lai
BACKGROUND: Of the three transforming growth factor (TGF)-β isoforms known, TGFβ1 deficits have been widely reported in Alzheimer's disease (AD) and studied as a potential therapeutic target. In contrast, the status of TGFβ2, which has been shown to mediate amyloid-β (Aβ)-mediated neuronal death, are unclear both in AD and in Lewy body dementias (LBD) with differential neuritic plaque and neurofibrillary tangle burden. OBJECTIVE: To measure neocortical TGFβ2 levels and their correlations with neuropathological and clinical markers of disease severity in a well-characterized cohort of AD as well as two clinical subtypes of LBD, dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), known to manifest relatively high and low Aβ plaque burden, respectively...
November 28, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27908423/copper-brain-protein-protection-against-free-radical-induced-neuronal-death-survival-ratio-in-sh-sy5y-neuroblastoma-cell-cultures
#14
Roger Deloncle, Bernard Fauconneau, Olivier Guillard, José Delaval, Gérard Lesage, Alain Pineau
In Creutzfeldt Jakob, Alzheimer and Parkinson diseases, copper metalloproteins such as prion, amyloid protein precursor and α-synuclein are able to protect against free radicals by reduction from cupric Cu(+2) to cupreous Cu(+). In these pathologies, a regional copper (Cu) brain decrease correlated with an iron, zinc or manganese (Mn) increase has previously been observed, leading to local neuronal death and abnormal deposition of these metalloproteins in β-sheet structures. In this study we demonstrate the protective effect of Cu metalloproteins against deleterious free-radical effects...
January 2017: Journal of Trace Elements in Medicine and Biology
https://www.readbyqxmd.com/read/27892477/nanomolar-oligomerization-and-selective-co-aggregation-of-%C3%AE-synuclein-pathogenic-mutants-revealed-by-single-molecule-fluorescence
#15
Emma Sierecki, Nichole Giles, Quill Bowden, Mark E Polinkovsky, Janina Steinbeck, Nicholas Arrioti, Diya Rahman, Akshay Bhumkar, Philip R Nicovich, Ian Ross, Robert G Parton, Till Böcking, Yann Gambin
Protein aggregation is a hallmark of many neurodegenerative diseases, notably Alzheimer's and Parkinson's disease. Parkinson's disease is characterized by the presence of Lewy bodies, abnormal aggregates mainly composed of α-synuclein. Moreover, cases of familial Parkinson's disease have been linked to mutations in α-synuclein. In this study, we compared the behavior of wild-type (WT) α-synuclein and five of its pathological mutants (A30P, E46K, H50Q, G51D and A53T). To this end, single-molecule fluorescence detection was coupled to cell-free protein expression to measure precisely the oligomerization of proteins without purification, denaturation or labelling steps...
November 28, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27890431/neuroprotective-mechanisms-of-plant-extracts-against-mptp-induced-neurotoxicity-future-applications-in-parkinson-s-disease
#16
REVIEW
Abdelrahman Ibrahim Abushouk, Ahmed Negida, Hussien Ahmed, Mohamed M Abdel-Daim
Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease, affecting about seven to 10 million patients worldwide. The major pathological features of PD are loss of dopaminergic neurons in the nigrostriatal pathway and accumulation of alpha-synuclein molecules, forming Lewy bodies. Until now, there is no effective cure for PD, and investigators are searching for neuroprotective strategies to stop or slow the disease progression. The MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) induced neurotoxicity of the nigrostriatal pathway has been used to initiate PD in animal models...
January 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27860405/flow-cytometric-screening-of-aggregation-inhibitors-using-a-fluorescence-assisted-intracellular-method
#17
Hanna Lindberg, Lisa Sandersjöö, Sebastian W Meister, Mathias Uhlén, John Löfblom, Stefan Ståhl
Aggregation of misfolded peptides and proteins is a key event in several neurodegenerative diseases. Suggested treatments of such disorders aim to inhibit the initial aggregation process. Here, we have developed an intracellular, function-based screening method, intended for isolation of aggregation-inhibitors from combinatorial protein libraries by flow-cytometric cell sorting. The method is based on fusion of aggregation-prone peptides to a fluorescent protein, functioning as a solubility reporter. Co-expression of a protein-based aggregation-inhibitor should prevent aggregation and thus increase the whole-cell fluorescence...
November 17, 2016: Biotechnology Journal
https://www.readbyqxmd.com/read/27859650/profile-of-cognitive-impairment-and-underlying-pathology-in-multiple-system-atrophy
#18
Shunsuke Koga, Adam Parks, Ryan J Uitti, Jay A van Gerpen, William P Cheshire, Zbigniew K Wszolek, Dennis W Dickson
BACKGROUND: The objectives of this study were to elucidate any potential association between α-synuclein pathology and cognitive impairment and to determine the profile of cognitive impairment in multiple system atrophy (MSA) patients. To do this, we analyzed the clinical and pathologic features in autopsy-confirmed MSA patients. METHODS: We retrospectively reviewed medical records, including neuropsychological test data, in 102 patients with autopsy-confirmed MSA in the Mayo Clinic brain bank...
November 15, 2016: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/27836779/contribution-of-cholesterol-and-oxysterols-to-the-pathophysiology-of-parkinson-s-disease
#19
REVIEW
Margaux Doria, Lucie Maugest, Thibault Moreau, Gérard Lizard, Anne Vejux
Neurodegenerative diseases are a major public health issue worldwide. Some countries, including France, have engaged in research into the causes of Parkinson's disease, Alzheimer's disease, and multiple sclerosis and the management of these patients. It should lead to a better understanding of the mechanisms leading to these diseases including the possible involvement of lipids in their pathogenesis. Parkinson's disease is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra and the accumulation of α-synuclein (Lewy bodies)...
December 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27824125/a-scfv-antibody-targeting-common-oligomeric-epitope-has-potential-for-treating-several-amyloidoses
#20
Jun Zha, Xiang-Meng Liu, Jie Zhu, Shu-Ying Liu, Shuai Lu, Peng-Xin Xu, Xiao-Lin Yu, Rui-Tian Liu
Overproduction or poor clearance of amyloids lead to amyloid aggregation and even amyloidosis development. Different amyloids may interact synergistically to promote their aggregation and accelerate pathology in amyloidoses. Amyloid oligomers assembled from different amyloids share common structures and epitopes, and are considered the most toxic species in the pathologic processes of amyloidoses, which suggests that an agent targeting the common epitope of toxic oligomers could provide benefit to several amyloidoses...
November 8, 2016: Scientific Reports
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