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subtypes parkinson

Fabian Maass, Isabel Schulz, Paul Lingor, Brit Mollenhauer, Mathias Bähr
In Parkinson's disease (PD), there is a wide field of recent and ongoing search for useful biomarkers for early and differential diagnosis, disease monitoring or subtype characterization. Up to now, no biofluid biomarker has entered the daily clinical routine. Cerebrospinal fluid (CSF) is often used as a source for biomarker development in different neurological disorders because it reflects changes in central-nervous system homeostasis. This review article gives an overview about different biomarker approaches in PD, mainly focusing on CSF analyses...
December 10, 2018: Molecular and Cellular Neurosciences
M B Adamson, G Gilmore, T W Stratton, N Baktash, M S Jog
BACKGROUND: Parkinson disease (PD) patients have turning impairments that may increase fall risk. Clinics lack specialized kinematic equipment used in gait and turn analysis and require a simple method to evaluate fall risk and advise patients in turning strategy selection. OBJECTIVES: To enhance understanding of PD turning strategies and determine if turning can be assessed using a video-recording and categorization method, we compared 180-degree and 90-degree turns as a function of medication status and dual-tasking (DT)...
November 22, 2018: Journal of the Neurological Sciences
Jinyoung Youn, Chung Lee, Eungseok Oh, Jinse Park, Ji Sun Kim, Hee-Tae Kim, Jin Whan Cho, Woong-Yang Park, Wooyoung Jang, Chang-Seok Ki
Early-onset Parkinson's disease (EOPD) can be linked to different genetic backgrounds depending on the disease characteristics. In Korean patients with EOPD, however, only 5 PARK genes have been tested. We recruited 70 patients with EOPD from 4 hospitals in Korea, and 12 PARK genes were screened via multigene panel sequencing. Large insertions or deletions were confirmed by multiplex ligation-dependent probe amplification. We found 20 rare variants (2 in SNCA, 2 in PRKN, 6 in LRRK2, 3 in PINK1, 1 in DJ1, 4 in FBX07, 1 in HTRA2, and 1 in EIG4G1) in 20 subjects regardless of heterogeneity...
November 7, 2018: Neurobiology of Aging
Dan Wang, Pratik Neupane, Lotten Ragnarsson, Robert J Capon, Richard J Lewis
T-type calcium channel (CaV 3.x) blockers are receiving increasing attention as potential therapeutics for the treatment of pathophysiological disorders and diseases, including absence epilepsy, Parkinson's disease (PD), hypertension, cardiovascular diseases, cancers, and pain. However, few clinically approved CaV 3.x blockers are available, and selective pharmacological tools are needed to further unravel the roles of individual CaV 3.x subtypes. In this work, through an efficient synthetic route to the marine fungal product pseudellone C, we obtained bisindole alkaloid analogs of pseudellone C with a modified tryptophan moiety and identified two CaV 3...
November 28, 2018: Marine Drugs
Samantha M Meadows, Melissa M Conti, Libby Gross, Nicole E Chambers, Yarden Avnor, Corinne Y Ostock, Kathryn Lanza, Christopher Bishop
BACKGROUND: The serotonergic system is a well-established modulator of l-dopa-induced dyskinesia. To date, targeting serotonin transporters or serotonin receptor subtype 1A (5-HT1A ) reduces l-dopa-induced dyskinesia in animal models; however, these strategies have failed to translate clinically. Ideally, a compound acting at both known antidyskinetic sites could optimize serotonin-mediated approaches. Vilazodone is a selective serotonin reuptake inhibitor and a partial 5-HT1A agonist approved by the U...
November 2018: Movement Disorders: Official Journal of the Movement Disorder Society
Lorraine V Kalia
Diagnostic biomarkers are measures that detect or confirm the presence of a disease or identify individuals with a subtype of the disease. For Parkinson's disease, unlike other neurodegenerative diseases such as Alzheimer's disease and Creutzfeldt-Jakob disease, diagnostic biomarkers remain elusive as none are yet available or approved for clinical use. A biomarker to diagnose early or prodromal Parkinson's disease with high accuracy would significantly enhance clinical practice as well as advance clinical therapeutic trials...
November 15, 2018: Parkinsonism & related Disorders
Michael Lawton, Yoav Ben-Shlomo, Margaret T May, Fahd Baig, Thomas R Barber, Johannes C Klein, Diane M A Swallow, Naveed Malek, Katherine A Grosset, Nin Bajaj, Roger A Barker, Nigel Williams, David J Burn, Thomas Foltynie, Huw R Morris, Nicholas W Wood, Donald G Grosset, Michele T M Hu
OBJECTIVES: To use a data-driven approach to determine the existence and natural history of subtypes of Parkinson's disease (PD) using two large independent cohorts of patients newly diagnosed with this condition. METHODS: 1601 and 944 patients with idiopathic PD, from Tracking Parkinson's and Discovery cohorts, respectively, were evaluated in motor, cognitive and non-motor domains at the baseline assessment. Patients were recently diagnosed at entry (within 3...
December 2018: Journal of Neurology, Neurosurgery, and Psychiatry
Tobias R Baumeister, Jowon L Kim, Maria Zhu, Martin J McKeown
BACKGROUND: White matter (WM) microstructural integrity is important for effective brain functioning and alterations have been shown in many neurodegenerative diseases. PURPOSE: To investigate WM myelin profiles and their relation to clinical features of Parkinson's disease (PD). STUDY TYPE: Retrospective cross-sectional. POPULATION: In all, 29 PD subjects and 15 healthy controls. FIELD STRENGTH/SEQUENCE: Multiecho GRASE with 10 msec echo spacing and echo planar imaging (EPI) diffusion-weighted (b-value = 700 with 32 gradient directions) on a 3T scanner...
November 15, 2018: Journal of Magnetic Resonance Imaging: JMRI
Danyan Chen, Jiehui Jiang, Ping Wu, Qihao Guo, Chuantao Zuo
Dementia has become a serious disease in elderly population. Graph theory based brain network analysis method is considered as a popular and universal technique in the field of the neurosciences. It can help neuroscientists to investigate the neuropathology of dementia, especially to understand dementia subtypes. However, brain network analysis for various dementia subtypes at the same time is still limited. The aim at this study is to investigate the similarities and differences in brain network modular parameters of three dementia subtypes: Alzheimer's disease (AD), Parkinson's disease dementia (PDD), Lewy body dementia (DLB)...
July 2018: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
Hucheng Zhou, Jiehui Jiang, Ping Wu, Qihao Guo, Chuantao Zuo
The clinical manifestation of Lewy body dementia (DLB) is distinct from Alzheimer's disease (AD), but overlap with Parkinson's disease dementia (PDD). However, little is known about different topology properties of abnormal brain networks associated with these neurodegenerative diseases. In order to study the difference of brain networks in various dementia subtypes, we used $^{\mathbf {18}}\text{F}$-Fluorodeoxyglucose positron emission tomography ($^{\mathbf {18}}\text{F}$-FDG PET) images and graph theory methods to investigate altered whole-brain intrinsic glucose metabolic functional networks in three Chinese dementia groups compared to healthy control (HC) group, including 22 AD patients, 18 PDD patients, 22 DLB patients and 22 HC subjects from Huashan Hospital, Shanghai, China...
July 2018: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
Jennifer E Davoren, Deane M Nason, Jotham Coe, Keith Dlugolenski, Christopher J Helal, Anthony R Harris, Erik LaChapelle, Sidney Liang, Yue Liu, Rebecca E O'Connor, Christine C Orozco, Brajesh Kumar Rai, Michelle Salafia, Brian M Samas, Wenjian Xu, Rouba Kozak, David Gray
The discovery of D1 subtype-selective agonists with drug-like properties has been an enduring challenge for the greater part of 40 years. All known D1-selective agonists are catecholamines which bring about receptor desensitization and undergo rapid metabolism thus limiting their utility as a therapeutic for chronic illness such as Schizophrenia and Parkinson's disease. Our high-throughput screening efforts on D1 yielded a single non-catecholamine hit, PF-4211 (6) that was developed into a series of potent D1 receptor agonist leads with high oral bioavailability and CNS penetration...
November 15, 2018: Journal of Medicinal Chemistry
Jeong Yeob Baek, Jae Yeong Jeong, Kyoung In Kim, So-Yoon Won, Young Cheul Chung, Jin Han Nam, Eun Ju Cho, Tae-Beom Ahn, Eugene Bok, Won-Ho Shin, Byung Kwan Jin
We demonstrated that capsaicin (CAP), an agonist of transient receptor potential vanilloid subtype 1 (TRPV1), inhibits microglia activation and microglia-derived oxidative stress in the substantia nigra (SN) of MPP⁺-lesioned rat. However, the detailed mechanisms how microglia-derived oxidative stress is regulated by CAP remain to be determined. Here we report that ciliary neurotrophic factor (CNTF) endogenously produced by CAP-activated astrocytes through TRPV1, but not microglia, inhibits microglial activation and microglia-derived oxidative stress, as assessed by OX-6 and OX-42 immunostaining and hydroethidine staining, respectively, resulting in neuroprotection...
November 10, 2018: International Journal of Molecular Sciences
Kyeong Joon Kim, Yun Jung Bae, Jong-Min Kim, Beom Joon Kim, Eung Seok Oh, Ji Young Yun, Ji Seon Kim, Han-Joon Kim
Background: Cerebral microbleeds (CMBs) are associated with cerebrovascular risk factors and cognitive dysfunction among patients with Parkinson's disease (PD). However, whether CMBs themselves are associated with PD is to be elucidated. Methods: We analyzed the presence of CMBs using 3-Tesla brain magnetic resonance imaging in non-demented patients with PD and in age-, sex-, and hypertension-matched control subjects. PD patients were classified according to their motor subtypes: tremor-dominant, intermediate, and postural instability-gait disturbance (PIGD)...
November 12, 2018: Journal of Korean Medical Science
Alexander Yitbarek, Khaled Taha-Abdelaziz, Douglas C Hodgins, Leah Read, Éva Nagy, J Scott Weese, Jeff L Caswell, John Parkinson, Shayan Sharif
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
October 31, 2018: Scientific Reports
Feng Luo, Linda H Kim, Philippe Magown, M Sohail Noor, Zelma Ht Kiss
Deep brain stimulation (DBS) of the globus pallidus pars interna (GPi) is a highly effective therapy for movement disorders, yet its mechanism of action remains controversial. Inhibition of local neurons due to release of GABA from afferents to the GPi is a proposed mechanism in patients. Yet, high frequency stimulation (HFS) produces prolonged membrane depolarization mediated by cholinergic neurotransmission in endopeduncular neurons (EP, GPi-equivalent in rodent). We applied HFS while recording neuronal firing from an adjacent electrode during microelectrode mapping of GPi in awake patients (both male and female) with Parkinson disease (PD) and dystonia...
October 29, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Ghilsoo Nam
T-type calcium channels are attractive targets for potential treatment of epilepsy inflammatory or neuropathic pain, insomnia, Parkinson's disease, and cancer. Three isoforms having different biophysical functions are expressed in peripheral and central nerve. Since the withdrawal of mibefradil, the first compound marketed for selective T-type calcium channel blockade, extensive efforts have been made to identify more selective T-type calcium channel blockers. Areas covered: This review covers the 43 patents describing 'organic small molecules as T-type calcium channel blockers'-published since 2012...
October 29, 2018: Expert Opinion on Therapeutic Patents
Dong-Mei Wu, Shan Wang, Xin Wen, Xin-Rui Han, Yong-Jian Wang, Min Shen, Shao-Hua Fan, Juan Zhuang, Zi-Feng Zhang, Qun Shan, Meng-Qiu Li, Bin Hu, Chun-Hui Sun, Jun Lu, Gui-Quan Chen, Yuan-Lin Zheng
Development of effective therapeutic drugs for Parkinson's disease (PD) is of great importance. Aberrant microRNA (miRNA) expression has been identified in postmortem human PD brain samples, in vitro and in vivo PD models. However, the role of miR-342-3p in PD has been understudied. The study explores the effects of miR-342-3p on expression of glutamate (Glu) transporter, and dopaminergic neuron apoptosis and proliferation by targeting p21-activated kinase 1 (PAK1) through the Wnt signaling pathway in PD mice...
October 26, 2018: Journal of Cellular Physiology
Yu S Mironova, I A Zhukova, N G Zhukova, V M Alifirova, O P Izhboldina, A V Latypova
AIM: To measure the concentration of glutamate in the serum of patients with Parkinson's disease (PD) and determine its association with clinical variants of disease course. MATERIAL AND METHODS: One hundred and ten patients with PD and 90 healthy people were examined. Glutamate concentration in the blood serum was determined with a spectrophotometric method. RESULTS AND CONCLUSION: Patients with Parkinson's disease had significantly higher levels of serum glutamate compared with healthy subjects (p<0,0001)...
2018: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
Cuiping Xu, Ping Zhuang, Mark Hallett, Yuqing Zhang, Jianyu Li, Yongjie Li
Background and purpose: Subthalamic nucleus deep brain stimulation (STN DBS) is well established for the treatment of advanced Parkinson's disease (PD), substantially improving motor symptoms, quality of life, and reducing the long-term need for dopaminergic medication. However, whether chronic STN DBS produces different effects on PD motor subtypes is unknown. This retrospective study aimed to evaluate the long-term effects of STN DBS on the PD motor subtypes. Methods: Eighty patients undergoing STN DBS were included...
2018: Frontiers in Human Neuroscience
Yuan Jiang, Long Yan, Longkuo Xia, Xiaoyin Lu, Wenliang Zhu, Dewen Ding, Mingxia Du, Da Zhang, Hongmei Wang, Baoyang Hu
Human pluripotent stem cells hold great promise for improving regenerative medicine. However, a risk for tumor formation and difficulties in generating large amounts of subtype derivatives remain the major obstacles for clinical applications of stem cells. Here, we discovered that zinc finger E-box-binding homeobox 1 (ZEB1) is highly expressed upon differentiation of human embryonic stem cells (hESCs) into neuronal precursors. CRISPR/Cas9-mediated ZEB1 depletion did not impede neural fate commitment, but  prevented hESCs-derived neural precursors from differentiating into neurons, indicating that ZEB1 is required for neuronal differentiation...
October 18, 2018: Journal of Biological Chemistry
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