David G Standaert, Vardhaman Patel, Sonya J Snedecor, Sandeep Thakkar, Yash J Jalundhwala, Pavnit Kukreja, David Kratochvil, Yanjun Bao, Rajesh Pahwa
INTRODUCTION: To estimate the impact of carbidopa/levodopa enteral suspension (CLES) on key patient-centered outcomes in patients with advanced Parkinson's disease (PD). METHODS: A comprehensive literature review identified relevant studies, from which data were meta-analyzed over 3-month intervals up to 24 months. Patient-centered outcomes of interest included mean (95% CI) changes from baseline (Δ) in quality of life (QoL), measured using PD-specific (PDQ-8, PDQ-39) and generic (EQ-5D) instruments; activities of daily living (ADL), measured in On and Off states using UPDRS Part II; and motor symptoms (i...
March 23, 2021: Parkinsonism & related Disorders
Adam J Bindas, Subhash Kulkarni, Ryan A Koppes, Abigail N Koppes
Parkinson's disease (PD) is a common neurodegenerative disease characterized by a progressive loss of fine motor function that impacts 1-2 out of 1,000 people. PD occurs predominately late in life and lacks a definitive biomarker for early detection. Recent cross-disciplinary progress has implicated the gut as a potential origin of PD pathogenesis. The gut-origin hypothesis has motivated research on gut PD pathology and transmission to the brain, especially during the prodromal stage (10-20 years before motor symptom onset)...
April 12, 2021: Acta Biomaterialia
Liwen Zhang, Yijing He, Kecheng Lei, Zhuo Fang, Qian Li, Jun Su, Zhiyu Nie, Yichun Xu, Lingjing Jin
Parkinson's disease (PD) is slowly progressive. Due to the lack of specific and sensitive biomarkers, the majority of PD patients are in the advanced stages when diagnosed. This study aimed to investigate biomarkers for early PD diagnosis. We first selected differential mRNAs by analysis of a Gene Expression Omnibus (GEO) data set. Next, we performed RNA sequencing to select differential mRNAs. After an integrated analysis of GEO and RNAseq data, we identified the PD early diagnosis biomarkers associated with oxidative stress...
April 12, 2021: Neuroscience Letters
James M Fulcher, Aman Makaju, Ronald J Moore, Mowei Zhou, David A Bennett, Philip L De Jager, Wei-Jun Qian, Ljiljana Paša-Tolić, Vladislav A Petyuk
Proteomic investigations of Alzheimer's and Parkinson's disease have provided valuable insights into neurodegenerative disorders. Thus far, these investigations have largely been restricted to bottom-up approaches, hindering the degree to which one can characterize a protein's "intact" state. Top-down proteomics (TDP) overcomes this limitation; however, it is typically limited to observing only the most abundant proteoforms and of a relatively small size. Therefore, fractionation techniques are commonly used to reduce sample complexity...
April 15, 2021: Journal of Proteome Research
Sukanto Sarkar, A R Rajalakshmi, S Avudaiappan, S Eswaran
OBJECTIVE: The retina has been investigated as a gateway to assess the neurodegenerative changes in the brain. Schizophrenia is also conceptualized as a neurodegenerative disorder like Alzheimer's and Parkinson's disease. The current literature suggests reduced retinal nerve fibre layer (RNFL) thickness and macular thickness (MT), as a marker of neurodegeneration, in patient suffering from chronic schizophrenia. This study aims to compare RNFL thickness and MT in acute schizophrenic patients with age and sex matched healthy controls...
April 15, 2021: International Ophthalmology
Ambra Stefani, Alex Iranzo, Evi Holzknecht, Daniela Perra, Matilde Bongianni, Carles Gaig, Beatrice Heim, Monica Serradell, Luca Sacchetto, Alicia Garrido, Stefano Capaldi, Almudena Sánchez-Gómez, Maria Paola Cecchini, Sara Mariotto, Sergio Ferrari, Michele Fiorini, Joachim Schmutzhard, Pietro Cocchiara, Isabel Vilaseca, Lorenzo Brozzetti, Salvatore Monaco, M Jose Marti, Klaus Seppi, Eduardo Tolosa, Joan Santamaria, Birgit Högl, Werner Poewe, Gianluigi Zanusso
Isolated REM sleep behaviour disorder (RBD) is an early-stage α-synucleinopathy in most, if not all, affected subjects. Detection of pathological α-synuclein in peripheral tissues of patients with isolated RBD may identify those progressing to Parkinson's disease, dementia with Lewy bodies or multiple system atrophy, with the ultimate goal of testing preventive therapies. Real-time quaking-induced conversion (RT-QuIC) provided evidence of α-synuclein seeding activity in CSF and olfactory mucosa of patients with α-synucleinopathies...
April 14, 2021: Brain
Anna Andrzejewska, Sylwia Dabrowska, Barbara Lukomska, Miroslaw Janowski
Neurological disorders are becoming a growing burden as society ages, and there is a compelling need to address this spiraling problem. Stem cell-based regenerative medicine is becoming an increasingly attractive approach to designing therapies for such disorders. The unique characteristics of mesenchymal stem cells (MSCs) make them among the most sought after cell sources. Researchers have extensively studied the modulatory properties of MSCs and their engineering, labeling, and delivery methods to the brain...
April 2021: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
Wojciech Kozubski, Kevin Ong, Wioletta Waleszczyk, Matthew Zabel, Jolanta Dorszewska
Neural plasticity-the ability to alter a neuronal response to environmental stimuli-is an important factor in learning and memory. Short-term synaptic plasticity and long-term synaptic plasticity, including long-term potentiation and long-term depression, are the most-characterized models of learning and memory at the molecular and cellular level. These processes are often disrupted by neurodegeneration-induced dementias. Alzheimer's disease (AD) accounts for 50% of cases of dementia. Vascular dementia (VaD), Parkinson's disease dementia (PDD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD) constitute much of the remaining cases...
2021: Neural Plasticity
Lisa Mészáros, Markus J Riemenschneider, Heiko Gassner, Franz Marxreiter, Stephan von Hörsten, Alana Hoffmann, Jürgen Winkler
Multiple system atrophy (MSA) is a rare, but fatal atypical parkinsonian disorder. The prototypical pathological hallmark are oligodendroglial cytoplasmic inclusions (GCIs) containing alpha-synuclein (α-syn). Currently, two MSA phenotypes are classified: the parkinsonian (MSA-P) and the cerebellar subtype (MSA-C), clinically characterized by predominant parkinsonism or cerebellar ataxia, respectively. Previous studies have shown that the transgenic MSA mouse model overexpressing human α-syn controlled by the oligodendroglial myelin basic protein (MBP) promoter (MBP29-hα-syn mice) mirrors crucial characteristics of the MSA-P subtype...
April 14, 2021: Acta Neuropathologica Communications
Federica Perrone, Rita Cacace, Julie van der Zee, Christine Van Broeckhoven
Knowledge of the molecular etiology of neurodegenerative brain diseases (NBD) has substantially increased over the past three decades. Early genetic studies of NBD families identified rare and highly penetrant deleterious mutations in causal genes that segregate with disease. Large genome-wide association studies uncovered common genetic variants that influenced disease risk. Major developments in next-generation sequencing (NGS) technologies accelerated gene discoveries at an unprecedented rate and revealed novel pathways underlying NBD pathogenesis...
April 14, 2021: Genome Medicine
Lais M Oliveira, Marta Ruiz Lopez, Alexandre Boutet, Gavin J B Elias, Suneil K Kalia, Mojgan Hodaie, Andres M Lozano, Renato P Munhoz, Alfonso Fasano
BACKGROUND: Parkinson's Disease patients undergo time-consuming programming to refine stimulation parameters after deep brain stimulation surgery. OBJECTIVE: To assess whether the use of the advanced functions of a patient's programmer would facilitate programming of deep brain stimulation. METHODS: Thirty patients were randomly allocated to the use of advanced versus simple mode of the patient programmer in this single-centre, prospective, randomized, controlled study...
April 11, 2021: Brain Stimulation
Caiting Gan, Kewei Ma, Lina Wang, Qianqian Si, Min Wang, Yongsheng Yuan, Kezhong Zhang
BACKGROUND: Rapid eye movement (REM) sleep behavior disorder (RBD) is one of the common nonmotor symptoms of Parkinson's disease (PD), characterized by frequently occurring REM sleep without muscle atonia. Our aim was to explore dynamic network connection changes in PD patients with RBD. METHOD: On the basis of RBD screening questionnaire (RBDSQ), 126 PD patients were classified into those with probable RBD symptoms (PD-pRBD) and without probable RBD (PD-npRBD)...
April 11, 2021: Brain Research
Esmat Fathi, Jay M Yarbro, Ramin Homayouni
Since their discovery over two decades ago, the molecular and cellular functions of the NIPSNAP family of proteins (NIPSNAPs) have remained elusive until recently. NIPSNAPs interact with a variety of mitochondrial and cytoplasmic proteins. They have been implicated in multiple cellular processes and associated with different physiologic and pathologic conditions, including pain transmission, Parkinson's disease, and cancer. Recent evidence demonstrated a direct role for NIPSNAP1 and NIPSNAP2 proteins in regulation of mitophagy, a process that is critical for cellular health and maintenance...
April 14, 2021: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
Reini E N van der Welle, Rebekah Jobling, Christian Burns, Paolo Sanza, Jan A van der Beek, Alfonso Fasano, Lan Chen, Fried J Zwartkruis, Susan Zwakenberg, Edward F Griffin, Corlinda Ten Brink, Tineke Veenendaal, Nalan Liv, Conny M A van Ravenswaaij-Arts, Henny H Lemmink, Rolph Pfundt, Susan Blaser, Carolina Sepulveda, Andres M Lozano, Grace Yoon, Teresa Santiago-Sim, Cedric S Asensio, Guy A Caldwell, Kim A Caldwell, David Chitayat, Judith Klumperman
Vacuolar protein sorting 41 (VPS41) is as part of the Homotypic fusion and Protein Sorting (HOPS) complex required for lysosomal fusion events and, independent of HOPS, for regulated secretion. Here, we report three patients with compound heterozygous mutations in VPS41 (VPS41S285P and VPS41R662 * ; VPS41c.1423-2A>G and VPS41R662 * ) displaying neurodegeneration with ataxia and dystonia. Cellular consequences were investigated in patient fibroblasts and VPS41-depleted HeLa cells. All mutants prevented formation of a functional HOPS complex, causing delayed lysosomal delivery of endocytic and autophagic cargo...
April 14, 2021: EMBO Molecular Medicine
T Y Alhazzazi, F T Alghamdi
The use of dental stem cells (DSCs) has emerged as a promising new approach for therapeutic purposes to treat dental and non-dental diseases. Thus, the aim of this systematic review was to compile all current information on the role and clinical applications of DSCs in modern regenerative medical therapy. PubMed and Google Scholar electronic databases were used to search the literature for relevant studies after applying specific inclusion and exclusion criteria. The search included articles that were published from 2009 to 2019...
April 2021: Nigerian Journal of Clinical Practice
Seong-Ik Kim, Hyunhee Kim, Jin Woo Park, Ji-Hyun Choi, Han Joon Kim, Jae Kyung Won, Beomseok Jeon, Sung-Hye Park
We report an autopsy case of a 56-year-old male patient with the coexistence of dentatorubral-pallidoluysian atrophy (DRPLA) and Parkinson's disease (PD). He presented with gait instability and dysarthria for 10 years. The removed brain showed general atrophy (988 g) with depigmentation of the substantia nigra. The neocortex and deep gray matter, including the red nucleus, subthalamic nuclei, and globus pallidus, were atrophic, and grumose degeneration of the cerebellar dentate nucleus was observed. Polyglutamine- and p62-positive neuronal inclusions were present and widespread in the areas mentioned above...
April 13, 2021: Neuropathology: Official Journal of the Japanese Society of Neuropathology
Shanshan Cao, Jie Tang, Chunyi Liu, Yi Fang, Linyang Ji, Yingjiao Xu, Zhengping Chen
PURPOSE: The dopamine transporter (DAT) is a marker of the occurrence and development of Parkinson's disease (PD) and other diseases with nigrostriatal degeneration. 2β-Carbomethoxy-3β-(4-chlorophenyl)-8-(2-[18 F]-fluoroethyl)nortropane ([18 F]FECNT), an 18 F-labelled tropane derivative, was reported to be a useful positron-emitting probe for DAT. However, the rapid formation of brain-penetrating radioactive metabolites is an impediment to the proper quantitation of DAT in PET studies with [18 F]FECNT...
April 13, 2021: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
Craig Horbinski, Katelyn B Zumpf, Kathleen McCortney, Dean Eoannou
BACKGROUND: Parkinson's Disease (PD) is a highly prevalent neurodegenerative disease whose incidence is increasing with an aging population. One of the most serious manifestations of PD is gait instability, leading to falls and subsequent complications that can be debilitating, even fatal. Boxing therapy (BT) uses gait and balance exercises to improve ambulation in people with PD, though its efficacy has not yet been fully proven. METHODS: In the current longitudinal observational study, 98 participants with idiopathic PD underwent twice-weekly BT sessions...
April 7, 2021: Research square
Susana J Gutierrez-Luke, Amber N Juba, Giulia Bertolin, Lori M Buhlman
Here, we describe a protocol for comprehensive quantification of autophagosome recruitment to mitochondria as an early step in mitophagy. Data collected using this protocol can be useful in the study of neurodegenerative disease, cancer, and metabolism-related disorders using models in which co-expression of mito-GFP and mCherry-Atg8a is feasible. This protocol has the advantage of assessment in an in vivo model organism ( Drosophila melanogaster ), where tissue-specific mitophagy can be investigated. For complete details on the use and execution of this protocol, please refer to (Cackovic et al...
June 18, 2021: STAR protocols
Lin Cheng, Wei Zhang
Studies have confirmed that DJ-1 is associated with diseases associated with the nervous system, including Alzheimer's disease (AD). However, the role of DJ-1 in the pathogenesis of AD has not been clarified. To investigate the effect of DJ-1 on brain tissue damage and cognitive function in AD mice and its possible mechanism, 5XFAD transgenic mice were used as AD model mice and DJ-1 in the brain was overexpressed by transfection of a lentiviral containing a specific targeting DJ-1 gene into the bilateral hippocampus of mice...
June 2021: Experimental and Therapeutic Medicine
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