Giovanni Granato, Gianluca Baldassarre
Executive functions represent a set of processes in goal-directed cognition that depend on integrated cortical-basal ganglia brain systems and form the basis of flexible human behaviour. Several computational models have been proposed for studying cognitive flexibility as a key executive function and the Wisconsin card sorting test (WCST) that represents an important neuropsychological tool to investigate it. These models clarify important aspects that underlie cognitive flexibility, particularly decision-making, motor response, and feedback-dependent learning processes...
July 15, 2021: Neural Networks: the Official Journal of the International Neural Network Society
Cristian V A Munteanu, Gabriela N Chirițoiu, Marioara Chirițoiu, Simona Ghenea, Andrei-Jose Petrescu, Ștefana M Petrescu
Various pathologies result from disruptions to or stress of endoplasmic reticulum (ER) homeostasis, such as Parkinson's disease and most neurodegenerative illnesses, diabetes, pulmonary fibrosis, viral infections and cancers. A critical process in maintaining ER homeostasis is the selection of misfolded proteins by the ER quality-control system (ERQC) for destruction via ER-associated degradation (ERAD). One key protein proposed to act during the first steps of misfolded glycoprotein degradation is the ER degradation-enhancing α-mannosidase-like protein 2 (EDEM2)...
July 28, 2021: Molecular & Cellular Proteomics: MCP
Junwei Gong, Wenlong Zhang, Liuyan Ding, Mengran Zhang, Shaohui Zheng, Runfang Ma, Junyuan Tang, Wei Yi, Huaxi Xu, Yunlong Zhang
Oxidative stress damage plays a pivotal role in Parkinson's disease (PD) pathogenesis. Previously, we developed a blood brain barrier-penetrating peptide-based "Trojan Horse" strategy to deliver 4,4'-dimethoxychalcone (DMC) for PD therapy and revealed neuroprotective properties of DMC in a PD model; however, the underlying mechanisms remained unclear. Here, we report that DMC attenuated motor impairment, degeneration of DA neurons and α-synuclein aggregation in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and exogenous human α-synuclein-induced PD mouse models...
July 28, 2021: Free Radical Biology & Medicine
Koji Yamano, Waka Kojima
BACKGROUND: Perturbations in organellar health can lead to an accumulation of unwanted and/or damaged organelles that are toxic to the cell and which can contribute to the onset of neurodegenerative diseases such as Parkinson's disease. Mitochondrial health is particularly critical given the indispensable role the organelle has not only in adenosine triphosphate production but also other metabolic processes. Byproducts of oxidative respiration, such as reactive oxygen species, however, can negatively impact mitochondrial fitness...
July 28, 2021: Biochimica et Biophysica Acta. General Subjects
Wisberty J Gordián-Vélez, Dimple Chouhan, Rodrigo A España, H Isaac Chen, Jason A Burdick, John E Duda, D Kacy Cullen
Parkinson's disease is a neurodegenerative disease affecting around 10 million people worldwide. The death of dopaminergic neurons in the substantia nigra and the axonal fibers that constitute the nigrostriatal pathway leads to a loss of dopamine in the striatum that causes the motor symptoms of this disease. Traditional treatments have focused on reducing symptoms, while therapies with human fetal or stem cell-derived neurons have centered on implanting these cells in the striatum to restore its innervation...
July 28, 2021: Brain Research Bulletin
Weixing Xu, Yuze Qi, Yanjun Gao, Huihui Quan, Qingru Li, Hui Zhou, Jing Huang
BACKGROUND: Previous work indicated that benzo[a]pyrene (B(a)P) exposure in utero might adversely affect neurodevelopment and cause Parkinson's Disease (PD)-like symptoms. However, the effect of utero exposure to B(a)P on PD-like α-synucleinopathy and the mechanism under are unclear. OBJECTIVE: The A53T human alpha-synuclein (α-syn) transgenic mice (M83+/- ) were used in this study to gain insights into the role of B(a)P exposure in utero in the onset of α-syn pathology and neuronal damage...
July 28, 2021: Toxicology and Applied Pharmacology
Changqing Zheng, Feng Zhang
Parkinson's disease (PD) is a progressive and self-propelling neurodegenerative disorder, which is characterized by motor symptoms, such as rigidity, tremor, slowness of movement and problems with gait. These symptoms become worse over time. To date, Dopamine (DA) replacement therapy with 3, 4-dihydroxy-L-phenylalanine (L-DOPA) is still the most effective pharmacotherapy for motor symptoms of PD. Unfortunately, motor fluctuations consisting of wearing-off effect actions and dyskinesia tend to occur in a few years of starting L-DOPA...
July 28, 2021: Neurotoxicology
Sonat Pınar Kara, Bengü Altunan, Aysun Unal
INTRODUCTION: Alzheimer's disease (AD), and idiopathic Parkinson's disease (IPD) are the neurodegenerative diseases of the central nervous system (CNS). Cognitive impairment is on the forefront in AD. However, IPD is a movement disorder. Inflammation was suggested to have an effect in the pathophysiology of these two diseases. Neutrophil-lymphocyte ratio (NLR) was shown to be a possible marker showing the peripheral inflammation. We aimed to investigate the NLR of patiens with the diagnosis of AD, and IPD, and individuals with no neurodegenerative disease...
July 31, 2021: Neurological Sciences
Mite Mijalkov, Giovanni Volpe, Joana B Pereira
Parkinson's disease (PD) is a neurodegenerative disorder characterized by topological abnormalities in large-scale functional brain networks, which are commonly analyzed using undirected correlations in the activation signals between brain regions. This approach assumes simultaneous activation of brain regions, despite previous evidence showing that brain activation entails causality, with signals being typically generated in one region and then propagated to other ones. To address this limitation, here, we developed a new method to assess whole-brain directed functional connectivity in participants with PD and healthy controls using antisymmetric delayed correlations, which capture better this underlying causality...
July 30, 2021: Cerebral Cortex
I Šonský, P Vodička, K Vodičková Kepková, H Hansíková
Huntington's disease (HD), as well as Parkinson's disease and Alzheimer's disease, belong to a group of neurodegenerative diseases characterized by common features, such as the progressive loss of neurons and the presence of pathogenic forms of misfolded protein aggregates. A quality control system such as autophagy is crucial for the clearance of protein aggregates and dysfunctional organelles and thus essential for the maintenance of neuronal homeostasis. The constant high energy demand of neuronal tissue links neurodegeneration to mitochondria...
July 27, 2021: Neurochemistry International
Philip W Tipton, Daniel Kenney-Jung, Beth K Rush, Erik H Middlebrooks, David Nascene, Balvindar Singh, Shernan Holtan, Ernesto Ayala, Daniel F Broderick, Troy Lund, Zbigniew K Wszolek
BACKGROUND: Colony-stimulating factor-1 receptor (CSF1R)-related leukoencephalopathy is a rapidly progressive neurodegenerative disease for which there is currently no cure. Hematopoietic stem cell transplantation (HSCT) has been proposed as a disease-modifying treatment. OBJECTIVE: The objective of this study was to determine the effect of HSCT on disease progression. METHODS: We collected all available clinical data from a cohort of 7 patients with CSF1R-related leukoencephalopathy who underwent HSCT at our institutions...
July 30, 2021: Movement Disorders: Official Journal of the Movement Disorder Society
Aimee Rodica Chis, Alexandra Ioana Moatar, Cristina Dijmarescu, Cecilia Rosca, Ruxandra Julia Vorovenci, Inge Krabbendam, Amalia Dolga, Cristina Bejinar, Catalin Marian, Ioan Ovidiu Sirbu, Mihaela Simu
Parkinson's disease (PD) is the second most common neurodegenerative disorder among the elderly, the diagnostic and prognostic of which is based mostly on clinical signs. LevoDopa replacement is the gold standard therapy for PD, as it ameliorates the motor symptoms. However, it does not affect the progression of the disease and its long-term use triggers severe complications. There are no bona fide biomarkers for monitoring the patients' response to LevoDopa and predicting the efficacy of levodopa treatment...
July 30, 2021: Journal of Cellular and Molecular Medicine
Nouara Yahi, Coralie Di Scala, Henri Chahinian, Jacques Fantini
Parkinson's disease (PD) is a major neurodegenerative disorder which exhibits many of the characteristics of a pandemic. Current therapeutic strategies are centered on the dopaminergic system, with limited efficacy, so that a treatment that has a direct impact on the underlying disease pathogenesis is urgently needed. Although α-synuclein is a privileged target for such therapies, this protein has been in the past wrongly considered as exclusively intracellular, so that the impact of paracrine neurotoxicity mechanisms in PD have been largely ignored...
July 30, 2021: Glycoconjugate Journal
Masoud Etemadifar, Ali Aghababaei, Hosein Nouri, Parisa K Kargaran, Shaghayegh Mohammadi, Mehri Salari
BACKGROUND: Even within the most populous countries in the Middle East, such as Iran, autoimmune encephalitis cases have been rarely reported. OBJECTIVE: We aimed to describe the demographic, clinical, and paraclinical characteristics of Iranian patients with autoimmune encephalitis positive for anti-neuronal autoantibodies. METHODS: This cross-sectional study included all patients diagnosed with autoimmune encephalitis and referred to our hospital, in Isfahan, Iran, from March 2016 to May 2020...
July 30, 2021: Neurological Sciences
Maria Paola Cecchini, Elisa Mantovani, Angela Federico, Alice Zanini, Sarah Ottaviani, Carla Masala, Michele Tinazzi, Stefano Tamburin
Olfactory deficit is a widely documented non-motor symptom in Parkinson's disease (PD). Abnormal turning points trajectories through olfactory threshold testing have been recently reported in patients with olfactory dysfunction, who seem to adapt faster to olfactory stimuli, but data on PD patients are lacking. The aim of this study is to perform olfactory threshold test and explore the turning points trajectories in PD patients in comparison to normal controls. We recruited 59 PD patients without dementia, and no conditions that could influence evaluation of olfaction and cognition...
July 30, 2021: Journal of Neural Transmission
Simo Nuuttila, Mikael Eklund, Juho Joutsa, Elina Jaakkola, Elina Mäkinen, Emma A Honkanen, Kari Lindholm, Tommi Noponen, Toni Ihalainen, Kirsi Murtomäki, Tanja Nojonen, Reeta Levo, Tuomas Mertsalmi, Filip Scheperjans, Valtteri Kaasinen
Glabellar tap or reflex (GR) is an old bedside clinical test used in the diagnostics of Parkinson's disease (PD), but its diagnostic value is unclear. This study examines the diagnostic validity and reliability of GR in PD in relation to brain dopaminergic activity. GR was performed on 161 patients with PD, 47 patients with essential tremor (ET) and 40 healthy controls immediately prior to dopamine transporter (DAT) [123 I]FP-CIT SPECT scanning. The binding ratios were investigated with consideration of the GR result (normal/abnormal)...
July 30, 2021: Journal of Neural Transmission
Elisa Montanaro, Alberto Romagnolo, Margherita Fabbri, Carlo Alberto Artusi, Gabriele Imbalzano, Mario Giorgio Rizzone, Leonardo Lopiano, Maurizio Zibetti
BACKGROUND: Parkinson's disease (PD) is increasingly recognized as a multidimensional disorder, characterized by several non-motor symptoms, including disturbances of sleep and cognition. Current studies on the relationship between sleep problems and neuropsychological functions, mainly conducted in early to moderate PD patients, outline mixed results. In this study, we analysed the relationship between subjectively reported sleep alterations and cognitive functions in a large cohort of 181 advanced PD patients...
July 30, 2021: Journal of Neurology
Susanne Herbst, Patrick A Lewis
Since the discovery of mutations in leucine-rich repeat kinase 2 (LRRK2) as an underlying genetic cause for the development of Parkinson's disease (PD) in 2004 (Neuron 44, 601-607; Neuron 44, 595-600), and subsequent efforts to develop LRRK2 kinase inhibitors as a therapy for Parkinson's (Expert Opin. Ther. Targets 21, 751-753), elucidating the atomic resolution structure of LRRK2 has been a major goal of research into this protein. At over 250 kDa, the large size and complicated domain organisation of LRRK2 has made this a highly challenging target for structural biologists, however, a number of recent studies using both in vitro and in situ approaches (Nature 588, 344-349; Cell 182, 1508-1518...
July 30, 2021: Biochemical Journal
Marjan Talebi, Mohsen Talebi, Tahereh Farkhondeh, Dalia M Kopustinskiene, Jesus Simal-Gandara, Jurga Bernatoniene, Saeed Samarghandian
Neurological diseases are responsible for a large number of morbidities and mortalities in the world. Flavonoids are phytochemicals that possess various health-promoting impacts. Chrysin, a natural flavonoid isolated from diverse fruits, vegetables, and even mushrooms, has several pharmacological activities comprising antioxidant, anti-inflammatory, antiapoptotic, anticancer, and neuroprotective effects. The current study was designed to review the relationship between chrysin administration and neurological complications by discussing the feasible mechanism and signaling pathways...
July 16, 2021: Biomedicine & Pharmacotherapy
Xuehan Ren, Jeffrey Lin, Glenn T Stebbins, Christopher G Goetz, Sheng Luo
BACKGROUND: Predicting Parkinson's disease (PD) progression may enable better adaptive and targeted treatment planning. OBJECTIVE: Develop a prognostic model using multiple, easily acquired longitudinal measures to predict temporal clinical progression from Hoehn and Yahr (H&Y) stage 1 or 2 to stage 3 in early PD. METHODS: Predictive longitudinal measures of PD progression were identified by the joint modeling method. Measures were extracted by multivariate functional principal component analysis methods and used as covariates in Cox proportional hazards models...
July 30, 2021: Movement Disorders: Official Journal of the Movement Disorder Society
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