Read by QxMD icon Read

Motor neurone disease

Antonella Sferra, Fabiana Fattori, Teresa Rizza, Elsabetta Flex, Emanuele Bellacchio, Alessandro Bruselles, Stefania Petrini, Serena Cecchetti, Massimo Teson, Fabrizia Restaldi, Andrea Ciolfi, Filippo M Santorelli, Ginevra Zanni, Sabina Barresi, Claudia Castiglioni, Marco Tartaglia, Enrico Bertini
Microtubules participate in fundamental cellular processes, including chromosomal segregation and cell division, migration, and intracellular trafficking. Their proper function is required for correct central nervous system development and operative preservation, and mutations in genes coding tubulins, the constituting units of microtubules, underlie a family of neurodevelopmental and neurodegenerative diseases, collectively known as "tubulinopathies", characterized by a wide range of neuronal defects resulting from defective proliferation, migration, and function...
March 14, 2018: Human Molecular Genetics
Lívia H Morais, Daniela B Hara, Maíra A Bicca, Anicleto Poli, Reinaldo N Takahashi
The factors that trigger the pathophysiology of Parkinson's disease (PD) are unknown. However, it is suggested that environmental factors, such as exposure to pesticides, play an important role, in addition to genetic predisposition and aging. Early signs of PD can appear in the gastrointestinal (GI) tract and in the olfactory system, preceding the onset of motor impairments by many years. The present study assessed the effects of oral rotenone administration (30 mg/kg) in inducing GI and olfactory dysfunctions associated with PD in mice...
April 2018: Behavioural Pharmacology
Adam J Stark, Christopher T Smith, Kalen J Petersen, Paula Trujillo, Nelleke C van Wouwe, Manus J Donahue, Robert M Kessler, Ariel Y Deutch, David H Zald, Daniel O Claassen
Parkinson's disease (PD) is characterized by widespread degeneration of monoaminergic (especially dopaminergic) networks, manifesting with a number of both motor and non-motor symptoms. Regional alterations to dopamine D2/3 receptors in PD patients are documented in striatal and some extrastriatal areas, and medications that target D2/3 receptors can improve motor and non-motor symptoms. However, data regarding the combined pattern of D2/3 receptor binding in both striatal and extrastriatal regions in PD are limited...
2018: NeuroImage: Clinical
Sara Ekmark-Lewén, Veronica Lindström, Astrid Gumucio, Elisabeth Ihse, Anish Behere, Philipp J Kahle, Eva Nordström, Maria Eriksson, Anna Erlandsson, Joakim Bergström, Martin Ingelsson
Introduction: Intraneuronal inclusions of alpha-synuclein are commonly found in the brain of patients with Parkinson's disease and other α-synucleinopathies. The correlation between alpha-synuclein pathology and symptoms has been studied in various animal models. In (Thy-1)-h[A30P] alpha-synuclein transgenic mice, behavioral and motor abnormalities were reported from 12 and 15 months, respectively. The aim of this study was to investigate whether these mice also display symptoms at earlier time points...
March 2018: Brain and Behavior
Michela Ferrucci, Gloria Lazzeri, Marina Flaibani, Francesca Biagioni, Federica Cantini, Michele Madonna, Domenico Bucci, Fiona Limanaqi, Paola Soldani, Francesco Fornai
Counting motor neurons within the spinal cord and brainstem represents a seminal step to comprehend the anatomy and physiology of the final common pathway sourcing from the CNS. Motor neuron loss allows to assess the severity of motor neuron disorders while providing a tool to assess disease modifying effects. Counting motor neurons at first implies gold standard identification methods. In fact, motor neurons may occur within mixed nuclei housing a considerable amount of neurons other than motor neurons. In the present review, we analyse various approaches to count motor neurons emphasizing both the benefits and bias of each protocol...
March 14, 2018: Histology and Histopathology
Kevin C Kemp, Kelly Hares, Juliana Redondo, Amelia J Cook, Harry R Haynes, Bronwen R Burton, Mark A Pook, Claire M Rice, Neil J Scolding, Alastair Wilkins
OBJECTIVES: Friedreich's ataxia is an incurable inherited neurological disease caused by frataxin deficiency. Here we report the neuro-reparative effects of myeloablative allogeneic bone marrow transplantation in a humanised murine model of the disease. METHODS: Mice received a transplant of fluorescently-tagged sex mis-matched bone marrow cells expressing wild-type frataxin and were assessed at monthly intervals using a range of behavioural motor performance tests...
March 13, 2018: Annals of Neurology
Laurie Galvan, Laetitia Francelle, Marie-Claude Gaillard, Lucie de Longprez, Maria-Angeles Carrillo-de Sauvage, Géraldine Liot, Karine Cambon, Lev Stimmer, Sophie Luccantoni, Julien Flament, Julien Valette, Michel de Chaldée, Gwenaelle Auregan, Martine Guillermier, Charlène Joséphine, Fanny Petit, Caroline Jan, Margot Jarrige, Noëlle Dufour, Gilles Bonvento, Sandrine Humbert, Frédéric Saudou, Philippe Hantraye, Karine Merienne, Alexis-Pierre Bemelmans, Anselme L Perrier, Nicole Déglon, Emmanuel Brouillet
The neurobiological functions of a number of kinases expressed in the brain are unknown. Here, we report new findings on DCLK3 (doublecortin like kinase 3), which is preferentially expressed in neurons in the striatum and dentate gyrus. Its function has never been investigated. DCLK3 expression is markedly reduced in Huntington's disease. Recent data obtained in studies related to cancer suggest DCLK3 could have an anti-apoptotic effect. Thus, we hypothesized that early loss of DCLK3 in Huntington's disease may render striatal neurons more susceptible to mutant huntingtin (mHtt)...
March 9, 2018: Brain: a Journal of Neurology
Rodrigo Novaes Ferreira, Aline Silva de Miranda, Natalia Pessoa Rocha, Ana Cristina Simoes E Silva, Antonio Lucio Teixeira, Elizabeth Ribeiro da Silva Camargos
BACKGROUND: Parkinson´s Disease (PD) is a chronic, progressive condition, being the second most common neurodegenerative disorder worldwide. The classical features include: bradykinesia, resting tremor, rigidity and festination. These neurological alterations are probably due to the death of dopaminergic neurons in the substantia nigra pars compacta and consequent reduction of dopamine input into the striatum. The decrease of dopamine levels may also be involved in the emergence of non-motor symptoms, including cognitive impairment, anxiety and depression symptoms...
March 12, 2018: Current Medicinal Chemistry
Yukie Kushimura, Takahiko Tokuda, Yumiko Azuma, Itaru Yamamoto, Ikuko Mizuta, Toshiki Mizuno, Masanori Nakagawa, Morio Ueyama, Yoshitaka Nagai, Hideki Yoshida, Masamitsu Yamaguchi
Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease characterized by the motor neuron degeneration that eventually leads to complete paralysis and death within 2-5 years after disease onset. One of the major pathological hallmark of ALS is abnormal accumulation of inclusions containing TAR DNA-binding protein-43 (TDP-43). TDP-43 is normally found in the nucleus, but in ALS, it localizes in the cytoplasm as inclusions as well as in the nucleus. Loss of nuclear TDP-43 functions likely contributes to neurodegeneration...
2018: American Journal of Neurodegenerative Disease
Huan Yi, Bingbing Xie, Ben Liu, Xuan Wang, Li Xu, Jia Liu, Min Li, Xiufeng Zhong, Fuhua Peng
Induced pluripotent stem cells (iPSCs) have provided new opportunities for motor neuron disease (MND) modeling, drug screening, and cellular therapeutic development. Among the various types of iPSCs, urine-derived iPSCs have become a promising source of stem cells because they can be safely and noninvasively isolated and easily reprogrammed. Here, for the first time, we differentiated urine-derived iPSCs (urine-iPSCs) into motor neurons (MNs) and compared the capacity of urine-iPSCs and cord-blood-derived iPSCs (B-iPSCs) to differentiate into MNs...
2018: Stem Cells International
Claude Rouillard, Joanie Baillargeon, Brigitte Paquet, Michel St-Hilaire, Jérôme Maheux, Catherine Lévesque, Noémie Darlix, Simon Majeur, Daniel Lévesque
Parkinson's disease (PD) is an idiopathic progressive neurodegenerative disorder characterized by the loss of midbrain dopamine neurons. Levodopa (l-dopa) is the main pharmacological approach to relieve PD motor symptoms. However, chronic treatment with l-Dopa is inevitably associated with the generation of abnormal involuntary movements (l-Dopa-induced dyskinesia). We have previously shown that Nr4a1 (Nur77), a transcription factor of the nuclear receptor family, is closely associated with dopamine neurotransmission in the mature brain...
March 9, 2018: Experimental Neurology
Lilian A Martinez Carrera, Elke Gabriel, Colin Donohoe, Irmgard Hölker, Aruljothi Mariappan, Markus Storbeck, Mirka Uhlirova, Jay Gopalakrishnan, Brunhilde Wirth
BICD2 encodes a highly conserved motor adaptor protein that regulates the dynein-dynactin complex in different cellular processes. Heterozygous mutations in BICD2 cause autosomal dominant lower extremity-predominant spinal muscular atrophy-2 (SMALED2). Although, various BICD2 mutations have been shown to alter interactions with different binding partners or the integrity of the Golgi apparatus, the specific pathological effects of BICD2 mutations underlying SMALED2 remain elusive. Here, we show that the fibroblasts derived from individuals with SMALED2 exhibit stable microtubules...
March 8, 2018: Human Molecular Genetics
Amrutha Swaminathan, Marilou Bouffard, Meijiang Liao, Sarah Ryan, Janis Bennion Callister, Stuart M Pickering-Brown, Gary Alan Barclay Armstrong, Pierre Drapeau
Large expansions of hexanucleotide GGGGCC (G4C2) repeats (hundreds to thousands) in the first intron of the chromosome 9 open reading frame 72 (C9orf72) locus are the strongest known genetic factor associated with amyotrophic lateral sclerosis and frontotemporal lobar degeneration (ALS/FTLD). Different hypotheses exist about the underlying disease mechanism including loss-of-function by haploinsufficiency, toxicity arising as a result of RNA or dipeptide repeats (DPRs). Five different DPRs are produced by repeat-associated non-ATG-initiated (RAN) translation of the G4C2 repeats...
March 8, 2018: Human Molecular Genetics
Hiroko Tsunekawa, Kazue Takahata, Motoki Okano, Toshiko Ishikawa, Hiroshi Satoyoshi, Tetsuya Nishimura, Naoya Hoshino, Shizuko Muraoka
3,4-Dihydroxy-L-phenylalanine (L-Dopa) remains the most effective drug for treating the motor symptoms of Parkinson's disease (PD). However, its long-term use is limited due to motor complications such as wearing-off and dyskinesia. A clinical study in PD patients with motor complications has demonstrated that selegiline, a monoamine oxidase type B inhibitor, is effective in reducing off time without worsening dyskinesia, although another study has shown worsening dyskinesia. Here, using unilateral 6-hydroxydopamine-lesioned rats showing degeneration of nigrostriatal dopaminergic neurons and L-Dopa-induced motor complications, we determined the efficacy of selegiline in controlling L-Dopa-induced motor fluctuations and exacerbated dyskinesia...
March 8, 2018: Behavioural Brain Research
Christina Andica, Koji Kamagata, Taku Hatano, Ayami Okuzumi, Asami Saito, Misaki Nakazawa, Ryo Ueda, Yumiko Motoi, Kouhei Kamiya, Michimasa Suzuki, Masaaki Hori, Kanako K Kumamaru, Nobutaka Hattori, Shigeki Aoki
INTRODUCTION: Parkinson's disease (PD) is marked by the degeneration of dopaminergic neurons in the nigrostriatal pathway (NSP). We aimed to identify the microstructural changes in the NSP of PD patients using neurite orientation dispersion and density imaging (NODDI). METHODS: NSPs of 29 PD patients, who were retrospectively selected from patients previously admitted to our institution, and 29 age- and gender-matched healthy controls were isolated via deterministic tractography...
February 28, 2018: Parkinsonism & related Disorders
T Gabriel Enge, Heath Ecroyd, Dianne F Jolley, Justin J Yerbury, Bernadett Kalmar, Anthony Dosseto
BACKGROUND: Amyotrophic lateral sclerosis (ALS) is among the most common of the motor neuron diseases, and arguably the most devastating. During the course of this fatal neurodegenerative disorder, motor neurons undergo progressive degeneration. The currently best-understood animal models of ALS are based on the over-expression of mutant isoforms of Cu/Zn superoxide dismutase 1 (SOD1); these indicate that there is a perturbation in metal homeostasis with disease progression. Copper metabolism in particular is affected in the central nervous system (CNS) and muscle tissue...
March 7, 2018: Molecular and Cellular Neurosciences
F Vitale, A Capozzo, P Mazzone, E Scarnati
The interest in the pedunculopontine tegmental nucleus (PPTg), a structure located in the brainstem at the level of the pontomesencephalic junction, has greatly increased in recent years because it is involved in the regulation of physiological functions that fail in Parkinson's disease and because it is a promising target for deep brain stimulation in movement disorders. The PPTg is highly interconnected with the main basal ganglia nuclei and relays basal ganglia activity to thalamic and brainstem nuclei and to spinal effectors...
March 7, 2018: Neurobiology of Disease
Alex Yen-Yu Chen, Tim Tully
Parkinson's disease (PD) is a progressive motor neurodegenerative disorder, characterized by a selective loss of dopaminergic neurons in the substantia nigra. The complexity of disease etiology includes both genetic and environmental factors. No effective drug that can modify disease progression and protect dopamine neurons from degeneration is presently available. Human α-Synuclein A30P (A30P) is a mutant gene identified in early onset PD and showed to result selective dopamine neuron loss in transgenic A30P flies and mice...
March 7, 2018: Neurobiology of Disease
Alejandro López-Hurtado, Daniel F Burgos, Paz González, Xose M Dopazo, Valentina González, Alberto Rábano, Britt Mellström, Jose R Naranjo
The transcriptional repressor DREAM (downstream regulatory element antagonist modulator) is a multifunctional neuronal calcium sensor (NCS) that controls Ca2+ and protein homeostasis through gene regulation and protein-protein interactions. Downregulation of DREAM is part of an endogenous neuroprotective mechanism that improves ATF6 (activating transcription factor 6) processing, neuronal survival in the striatum, and motor coordination in R6/2 mice, a model of Huntington's disease (HD). Whether modulation of DREAM activity can also ameliorate cognition deficits in HD mice has not been studied...
March 9, 2018: Molecular Brain
Charlotte Ridler
No abstract text is available yet for this article.
March 9, 2018: Nature Reviews. Neurology
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"