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https://www.readbyqxmd.com/read/28214539/lumbee-traditional-medicine-neuroprotective-activities-of-medicinal-plants-used-to-treat-parkinson-s-disease-related-symptoms
#1
Aurélie de Rus Jacquet, Michael Timmers, Sin Ying Ma, Andrew Thieme, George P McCabe, Jay Hansford C Vest, Mary Ann Lila, Jean-Christophe Rochet
ETHNOPHARMACOLOGICAL RELEVANCE: Parkinson's disease (PD) is a neurodegenerative disorder characterized by a loss of dopaminergic neurons in the substantia nigra pars compacta and the presence in surviving neurons of Lewy body inclusions enriched with aggregated forms of the presynaptic protein α-synuclein (aSyn). Although current therapies provide temporary symptomatic relief, they do not slow the underlying neurodegeneration in the midbrain. In this study, we analyzed contemporary herbal medicinal practices used by members of the Lumbee tribe to treat PD-related symptoms, in an effort to identify safe and effective herbal medicines to treat PD...
February 15, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28214264/identification-of-candidate-cerebrospinal-fluid-biomarkers-in-parkinsonism-using-quantitative-proteomics
#2
N K Magdalinou, A J Noyce, R Pinto, E Lindstrom, J Holmén-Larsson, M Holtta, K Blennow, H R Morris, T Skillbäck, T T Warner, A J Lees, I Pike, M Ward, H Zetterberg, J Gobom
INTRODUCTION: Neurodegenerative parkinsonian syndromes have significant clinical and pathological overlap, making early diagnosis difficult. Cerebrospinal fluid (CSF) biomarkers may aid the differentiation of these disorders, but other than α-synuclein and neurofilament light chain protein, which have limited diagnostic power, specific protein biomarkers remain elusive. OBJECTIVES: To study disease mechanisms and identify possible CSF diagnostic biomarkers through discovery proteomics, which discriminate parkinsonian syndromes from healthy controls...
January 31, 2017: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/28213435/genetics-of-synucleinopathies
#3
Robert L Nussbaum
Parkinson's disease (PD), diffuse Lewy body disease (DLBD), and multiple system atrophy (MSA) constitute the three major neurodegenerative disorders referred to as synucleinopathies because both genetic and pathological results implicate the α-synuclein protein in their pathogenesis. PD and DLBD are recognized as closely related diseases with substantial clinical and pathological overlap. MSA, on the other hand, has a distinctive clinical presentation and neuropathological profile. In this review, we will summarize the evidence linking α-synuclein to these three disorders...
February 17, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28213071/pla2g6-accumulates-in-lewy-bodies-in-park14-and-idiopathic-parkinson-s-disease
#4
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/28212433/elevated-gm3-plasma-concentration-in-idiopathic-parkinson-s-disease-a-lipidomic-analysis
#5
Robin B Chan, Adler J Perotte, Bowen Zhou, Christopher Liong, Evan J Shorr, Karen S Marder, Un J Kang, Cheryl H Waters, Oren A Levy, Yimeng Xu, Hong Bin Shim, Itsik Pe'er, Gilbert Di Paolo, Roy N Alcalay
Parkinson's disease (PD) is a common neurodegenerative disease whose pathological hallmark is the accumulation of intracellular α-synuclein aggregates in Lewy bodies. Lipid metabolism dysregulation may play a significant role in PD pathogenesis; however, large plasma lipidomic studies in PD are lacking. In the current study, we analyzed the lipidomic profile of plasma obtained from 150 idiopathic PD patients and 100 controls, taken from the 'Spot' study at Columbia University Medical Center in New York. Our mass spectrometry based analytical panel consisted of 520 lipid species from 39 lipid subclasses including all major classes of glycerophospholipids, sphingolipids, glycerolipids and sterols...
2017: PloS One
https://www.readbyqxmd.com/read/28208742/aav-vector-mediated-gene-delivery-to-substantia-nigra-dopamine-neurons-implications-for-gene-therapy-and-disease-models
#6
REVIEW
Katrina Albert, Merja H Voutilainen, Andrii Domanskyi, Mikko Airavaara
Gene delivery using adeno-associated virus (AAV) vectors is a widely used method to transduce neurons in the brain, especially due to its safety, efficacy, and long-lasting expression. In addition, by varying AAV serotype, promotor, and titer, it is possible to affect the cell specificity of expression or the expression levels of the protein of interest. Dopamine neurons in the substantia nigra projecting to the striatum, comprising the nigrostriatal pathway, are involved in movement control and degenerate in Parkinson's disease...
February 8, 2017: Genes
https://www.readbyqxmd.com/read/28202824/-disease-modifying-therapy-for-parkinson-s-disease
#7
Hideki Shimura, Nobutaka Hattori
Currently, treatment of Parkinson's disease aims at alleviating its symptoms. However development of disease-modifying drugs has been a remarkable advancement in recent years. Furthermore, clinical trials of immunotherapy against α-synuclein, a protein involved in the pathogenesis of and lesion expansion in Parkinson's disease, have been initiated. Here, the disease-modifying treatment for patients with Parkinson's disease including the current α-synuclein immunotherapy, gene therapy, protein injection therapy, and cell transplantation therapy, has been reviewed...
February 2017: Brain and Nerve, Shinkei Kenkyū No Shinpo
https://www.readbyqxmd.com/read/28202670/mechanisms-of-lrrk2-dependent-neurodegeneration-role-of-enzymatic-activity-and-protein-aggregation
#8
REVIEW
Md Shariful Islam, Darren J Moore
Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common cause of familial Parkinson's disease (PD) with autosomal dominant inheritance. Accordingly, LRRK2 has emerged as a promising therapeutic target for disease modification in PD. Since the first discovery of LRRK2 mutations some 12 years ago, LRRK2 has been the subject of intense investigation. It has been established that LRRK2 can function as a protein kinase, with many putative substrates identified, and can also function as a GTPase that may serve in part to regulate kinase activity...
February 8, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28197125/rna-interference-of-human-%C3%AE-synuclein-in-mouse
#9
Young-Cho Kim, Adam Miller, Livia C R F Lins, Sang-Woo Han, Megan S Keiser, Ryan L Boudreau, Beverly L Davidson, Nandakumar S Narayanan
α-Synuclein is postulated to play a key role in the pathogenesis of Parkinson's disease (PD). Aggregates of α-synuclein contribute to neurodegeneration and cell death in humans and in mouse models of PD. Here, we use virally mediated RNA interference to knockdown human α-synuclein in mice. We used an siRNA design algorithm to identify eight siRNA sequences with minimal off-targeting potential. One RNA-interference sequence (miSyn4) showed maximal protein knockdown potential in vitro. We then designed AAV vectors expressing miSyn4 and injected them into the mouse substantia nigra...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28197072/hmgb1-mediates-autophagy-dysfunction-via-perturbing-beclin1-vps34-complex-in-dopaminergic-cell-model
#10
Jinsha Huang, Jiaolong Yang, Yan Shen, Haiyang Jiang, Chao Han, Guoxin Zhang, Ling Liu, Xiaoyun Xu, Jie Li, Zhicheng Lin, Nian Xiong, Zhentao Zhang, Jing Xiong, Tao Wang
Parkinson's disease (PD), a progressive neurodegenerative disorder, is characterized by irreversible dopaminergic neuron loss and intra-neuronal α-synuclein aggregation. High mobility group box 1 (HMGB1) has been proven to be involved in autophagy dysfunction induced by α-synuclein accumulation, and the Beclin1-vacuolar protein sorting 34 (Vps34) complex is of great importance to the initiation of autophagy. Nevertheless, the concrete interaction mechanism between HMGB1, α-synuclein and autophagy remains elusive, especially in the context of PD...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28195695/o-glcnacylation-of-%C3%AE-synuclein-at-serine-87-reduces-aggregation-without-affecting-membrane-binding
#11
Yuka E Lewis, Ana Galesic, Paul M Levine, Cesar A De Leon, Natalie Lamiri, Caroline K Brennan, Matthew R Pratt
The aggregation of neurodegenerative-disease associated proteins can be affected by many factors, including a variety of posttranslational modifications. One such modification, O-GlcNAcylation, has been found on some of these aggregation prone proteins, including α-synuclein, the major protein that plays a causative role in synucleinopathies like Parkinson's disease. We previously used synthetic protein chemistry to prepare α-synuclein bearing an homogeneous O-GlcNAc modification at threonine 72 and showed that this modification inhibits protein aggregation...
February 14, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28193887/tmem175-deficiency-impairs-lysosomal-and-mitochondrial-function-and-increases-%C3%AE-synuclein-aggregation
#12
Sarah Jinn, Robert E Drolet, Paige E Cramer, Andus Hon-Kit Wong, Dawn M Toolan, Cheryl A Gretzula, Bhavya Voleti, Galya Vassileva, Jyoti Disa, Marija Tadin-Strapps, David J Stone
Parkinson disease (PD) is a neurodegenerative disorder pathologically characterized by nigrostriatal dopamine neuron loss and the postmortem presence of Lewy bodies, depositions of insoluble α-synuclein, and other proteins that likely contribute to cellular toxicity and death during the disease. Genetic and biochemical studies have implicated impaired lysosomal and mitochondrial function in the pathogenesis of PD. Transmembrane protein 175 (TMEM175), the lysosomal K(+) channel, is centered under a major genome-wide association studies peak for PD, making it a potential candidate risk factor for the disease...
February 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28192290/site-specific-structural-dynamics-of-%C3%AE-synuclein-revealed-by-time-resolved-fluorescence-spectroscopy-a-review
#13
Shruti Sahay, G Krishnamoorthy, Samir K Maji
Aggregation of α-Synuclein (α-Syn) into amyloid fibrils is known to be associated with the pathogenesis of Parkinson's disease (PD). Several missense mutations of the α-Syn gene have been associated with rare, early onset familial forms of PD. Despite several studies done so far, the local/residue-level structure and dynamics of α-Syn in its soluble and aggregated fibril form and how these are affected by the familial PD associated mutations are still not clearly understood. Here, we review studies performed by our group as well as other research groups, where time-resolved fluorescence spectroscopy has been used to understand the site-specific structure and dynamics of α-Syn under physiological conditions as well as under conditions that alter the aggregation properties of the protein such as low pH, high temperature, presence of membrane mimics and familial PD associated mutations...
October 11, 2016: Methods and Applications in Fluorescence
https://www.readbyqxmd.com/read/28187263/tetrahydroxystilbene-glucoside-inhibits-%C3%AE-synuclein-aggregation-and-apoptosis-in-a53t-%C3%AE-synuclein-transfected-cells-exposed-to-mpp-sup-sup
#14
Ruyi Zhang, Fangling Sun, Lan Zhang, Xuejing Sun, Lin Li
Increasing evidence has solidified the involvement of α-synuclein (α-Syn) and neurotoxins in the pathogenesis of Parkinson's disease (PD), suggesting a combination of genetic and environmental influences. 2,3,5,4'-Tetrahydroxystilbene -2-O-β-D-glucoside (TSG) is one of the main active components extracted from Polygonum multiflorum. The purpose of the present study was to investigate the effects of TSG on α-Syn aggregation, mitochondrial dysfunction, oxidative stress and apoptosis in vitro. A53T mutant α-synuclein-transfected cells (A53T AS cells) plus MPP+<sup></sup> exposure were used as a complex cell model of PD...
February 10, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28181693/frontotemporal-lobar-degeneration-tdp-with-multiple-system-atrophy-phenocopy-syndrome
#15
Ana Luísa Sousa, Ricardo Taipa, Niall Quinn, Tamas Revesz, Manuel Melo Pires, Marina Magalhães
Multiple system atrophy (MSA) is a neurodegenerative disorder presenting with parkinsonism, cerebellar involvement, autonomic dysfunction and pyramidal signs (1). Two main clinical subtypes of MSA are recognized: a parkinsonian-type (MSA-P) associated with predominant nigrostriatal degeneration and a cerebellar-type (MSA-C) with predominant olivopontocerebellar atrophy. A 'definite' diagnosis requires pathological confirmation with demonstration of glial cytoplasmic inclusions comprising alpha-synuclein protein aggregates (1)...
February 9, 2017: Neuropathology and Applied Neurobiology
https://www.readbyqxmd.com/read/28181068/laminar-degeneration-of-frontal-and-temporal-cortex-in-parkinson-disease-dementia
#16
Richard A Armstrong
To investigate cortical laminar degeneration in Parkinson's disease (PD) with dementia (PDD). Changes in density of α-synuclein-immunoreactive Lewy bodies (LB), Lewy neurites (LN), and Lewy grains (LG) together with surviving neurons, abnormally enlarged neurons (EN), vacuoles, and glial cell nuclei were measured across cortical laminae of frontal and temporal cortex in fifteen cases of PDD using quantitative methods and polynomial curve-fitting. Most frequently, LB and LN were distributed across all laminae, while LG were distributed in upper cortical laminae...
February 8, 2017: Neurological Sciences
https://www.readbyqxmd.com/read/28180961/dermal-phospho-alpha-synuclein-deposits-confirm-rem-sleep-behaviour-disorder-as-prodromal-parkinson-s-disease
#17
Kathrin Doppler, Hanna-Maria Jentschke, Lena Schulmeyer, David Vadasz, Annette Janzen, Markus Luster, Helmut Höffken, Geert Mayer, Joachim Brumberg, Jan Booij, Thomas Musacchio, Stephan Klebe, Elisabeth Sittig-Wiegand, Jens Volkmann, Claudia Sommer, Wolfgang H Oertel
Phosphorylated alpha-synuclein (p-alpha-syn) deposits, one of the neuropathological hallmarks of Parkinson's disease (PD), have recently been detected in dermal nerve fibres in PD patients with good specificity and sensitivity. Here, we studied whether p-alpha-syn may serve as a biomarker in patients with a high risk of developing PD, such as those with REM sleep behaviour disorder (RBD). We compared the presence and distribution of p-alpha-syn deposits in dermal nerve fibres in 18 patients with RBD, 25 patients with early PD and 20 normal controls...
February 8, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28180219/super-resolution-imaging-of-alpha-synuclein-polymorphisms-and-their-potential-role-in-neurodegeneration
#18
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/28173842/hypomethylation-of-intron1-of-%C3%AE-synuclein-gene-does-not-correlate-with-parkinson-s-disease
#19
Subhrangshu Guhathakurta, Baggio A Evangelista, Susmita Ghosh, Sambuddha Basu, Yoon-Seong Kim
Deregulation of α-synuclein encoding gene (SNCA) is one of the important facets of Parkinson's disease (PD) research. DNA methylation status of SNCA-intron1 has been shown to regulate the α-synuclein expression. The present study is aimed at investigating whether methylation of SNCA-intron1 is associated with higher expression of α-synuclein in PD. We have investigated the intron1 methylation status from 16 post-mortem brain samples comprised of 8 PD and 8 control subjects using bisulfite sequencing. We further correlated this methylation status with α-synuclein protein levels in substantia nigra of that individual using western blot analysis...
February 7, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28170377/%C3%AE-synuclein-toxicity-in-neurodegeneration-mechanism-and-therapeutic-strategies
#20
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
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