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survival of motor neuron

Niamh Moriarty, Clare L Parish, Eilís Dowd
The dopamine precursor, levodopa, remains the 'gold-standard' treatment for Parkinson's disease, and, although it provides superlative efficacy in the early stages of the disease, its long-term use is limited by the development of severe motor side effects and a significant abating of therapeutic efficacy. Therefore, there remains a major unmet clinical need for the development of effective neuroprotective, neurorestorative or neuroreparatory therapies for this condition. The relatively selective loss of dopaminergic neurons from the nigrostriatal pathway makes Parkinson's disease an ideal candidate for reparative cell therapies wherein the dopaminergic neurons that are lost in the condition are replaced through direct cell transplantation into the brain...
June 20, 2018: European Journal of Neuroscience
Phillip L Price, Dmytro Morderer, Wilfried Rossoll
Spinal muscular atrophy (SMA) is a motor neuron disease caused by mutations/deletions within the survival of motor neuron 1 (SMN1) gene that lead to a pathological reduction of SMN protein levels. SMN is part of a multiprotein complex, functioning as a molecular chaperone that facilitates the assembly of spliceosomal small nuclear ribonucleoproteins (snRNP). In addition to its role in spliceosome formation, SMN has also been found to interact with mRNA-binding proteins (mRBPs), and facilitate their assembly into mRNP transport granules...
2018: Advances in Neurobiology
Ravindra N Singh, Natalia N Singh
Spinal muscular atrophy (SMA) is one of the major genetic disorders associated with infant mortality. More than 90% cases of SMA result from deletions or mutations of Survival Motor Neuron 1 (SMN1) gene. SMN2, a nearly identical copy of SMN1, does not compensate for the loss of SMN1 due to predominant skipping of exon 7. However, correction of SMN2 exon 7 splicing has proven to confer therapeutic benefits in SMA patients. The only approved drug for SMA is an antisense oligonucleotide (Spinraza™/Nusinersen), which corrects SMN2 exon 7 splicing by blocking intronic splicing silencer N1 (ISS-N1) located immediately downstream of exon 7...
2018: Advances in Neurobiology
Benjamin Gille, Maxim De Schaepdryver, Janne Goossens, Lieselot Dedeene, Joke De Vocht, Emanuela Oldoni, An Goris, Ludo Van Den Bosch, Bart Depreitere, Kristl G Claeys, Jos Tournoy, Philip Van Damme, Koen Poesen
AIMS: Amyotrophic Lateral Sclerosis (ALS) is the most common motor neuron degeneration disease with a diagnostic delay of about one year after symptoms onset. In ALS, blood neurofilament light chain (NfL) levels are elevated, but it is not entirely clear what drives this increase and what the diagnostic performance of serum NfL is in terms of predictive values and likelihood ratios. The aims of this study were to further explore the prognostic and diagnostic performances of serum NfL to discriminate between patients with ALS and ALS mimics, and to investigate the relationship between serum NfL with motor neuron degeneration...
June 16, 2018: Neuropathology and Applied Neurobiology
Giulia Costa, Annalisa Pinna, Pier Francesca Porceddu, Maria Antonietta Casu, Anna Di Maio, Francesco Napolitano, Alessandro Usiello, Micaela Morelli
We have recently shown that male Rhes knockout (KO) mice develop a mild form of spontaneous Parkinson's disease (PD)-like phenotype, characterized by motor impairment and a decrease in nigrostriatal dopamine (DA) neurons. Experimental evidence has implicated neuroinflammation in PD progression, and the presence of activated glial cells has been correlated with DA neuron degeneration. Despite this, several factors, such as gender, have been found to affect DAergic neuron degeneration and influence neuroinflammation, explaining the differences between men and women in the etiology of PD...
2018: Frontiers in Aging Neuroscience
Daniela Pletto, Silvia Capra, Adele Finardi, Francesca Colciaghi, Paola Nobili, Giorgio Stefano Battaglia, Denise Locatelli, Cinzia Cagnoli
Spinal Muscular Atrophy (SMA) is a severe autosomal recessive disease characterized by selective motor neuron degeneration, caused by disruptions of the Survival of Motor Neuron 1 (Smn1) gene. The main product of SMN1 is the full-length SMN protein (FL-SMN), that plays an established role in mRNA splicing. FL-SMN is also involved in neurite outgrowth and axonal transport. A shorter SMN isoform, axonal-SMN or a-SMN, displays a more specific axonal localization and has remarkable axonogenic properties in NSC-34...
2018: PloS One
Serena Stanga, Liliana Brambilla, Bernadette Tasiaux, Anh H Dang, Adrian Ivanoiu, Jean-Noël Octave, Daniela Rossi, Vincent van Pesch, Pascal Kienlen-Campard
The current inability of clinical criteria to accurately identify the "at-risk group" for Amyotrophic Lateral Sclerosis (ALS) development as well as its unknown etiology are fueling the interest in biomarkers aimed at completing clinical approaches for the diagnosis. The Glial cell line-derived neurotrophic factor (GDNF) is a diffusible peptide critically involved in neuronal differentiation and survival. GDNF is largely studied in various neurological and neuromuscular diseases, with a great interest in the peripheral nervous system (PNS)...
2018: Frontiers in Neurology
Robert Smigiel, Gerd Landsberg, Maximilian Schilling, Małgorzata Rydzanicz, Agnieszka Pollak, Anna Walczak, Anna Stodolak, Piotr Stawinski, Hanna Mierzewska, Maria M Sasiadek, Oliver J Gruss, Rafal Ploski
PTPN23 encodes a ubiquitously expressed non-receptor type, catalytically inactive protein-tyrosine phosphatase found in all cells including neurons. Recently, we have identified PTPN23 in a cellular screen for the systematic identification of novel regulators of survival motor neuron (SMN) function in the assembly of splicing factors (Uridine-rich small nuclear ribonucleoproteins, UsnRNPs). Based on three families, recessive PTPN23 variants have been associated with human disease tentatively, without functional studies...
June 13, 2018: European Journal of Human Genetics: EJHG
Zhong-Ying Gong, Gao-Peng Lv, Li-Na Gao, Yi Lu, Jie Guo, Da-Wei Zang
BACKGROUND: There are no reliable biomarkers that could evaluate the disease burden in amyotrophic lateral sclerosis (ALS). OBJECTIVES: The aim of our study is to evaluate the changes in cerebrospinal fluid (CSF) and serum neurofilament subunit L (NF-L) in patients with ALS and to analyze the correlations between the levels of NF-L and clinical parameters. METHOD: CSF and serum samples were obtained from 80 ALS patients and 40 controls. The levels of NF-L in CSF and serum were assessed, and disease progression parameters including duration, revised ALS Functional Rating Scale (ALSFRS-r) score, disease progression rate (DPR), upper motor neuron (UMN) score, and survival were analyzed by registered neurologists...
June 13, 2018: Neuro-degenerative Diseases
Auriane Corbière, Marie-Laure Walet-Balieu, Philippe Chan, Magali Basille-Dugay, Julie Hardouin, David Vaudry
The cerebellum is a brain structure involved in motor and cognitive functions. The development of the cerebellar cortex (the external part of the cerebellum) is under the control of numerous factors. Among these factors, neuropeptides including PACAP or somatostatin modulate the survival, migration and/or differentiation of cerebellar granule cells. Interestingly, such peptides contributing to cerebellar ontogenesis usually exhibit a specific transient expression profile with a low abundance at birth, a high expression level during the developmental processes, which take place within the first two postnatal weeks in rodents, and a gradual decline toward adulthood...
June 12, 2018: Molecular & Cellular Proteomics: MCP
Beppe Aquilina, Ruben J Cauchi
OBJECTIVE: Spinal muscular atrophy (SMA) results from insufficient levels of the survival motor neuron (SMN) protein. Drosophila is conducive to large-scale genetic-modifier screens which can reveal novel pathways underpinning the disease mechanism. We tested the ability of a large collection of genomic deletions to enhance SMN-dependent lethality. To test our design, we asked whether our study can identify loci containing genes identified in previous genetic screens. Our objective was to find a common link between genes flagged in independent screens, which would allow us to expose novel functions for SMN in vivo...
June 13, 2018: BMC Research Notes
Shimaa Eissa, Nawal Alshehri, Mai Abduljabbar, Anas M Abdel Rahman, Majed Dasouki, Imran Y Nizami, Mohammad A Al-Muhaizea, Mohammed Zourob
Simultaneous and point-of-care detection of multiple protein biomarkers has significant impact on patient care. Spinal Muscular Atrophy (SMA), Cystic Fibrosis (CF) and Duchenne Muscular Dystrophy (DMD) are well known progressive hereditary disorders associated with increased morbidity as well as mortality. Therefore, rapid detection of biomarkers specific for these three disorders in newborns offers new opportunities for early diagnosis, delaying symptoms and effective treatment. Here, we report the development of a disposable carbon nanofiber (CNF)-based electrochemical immunosensor for simultaneous detection of survival motor neuron 1 (SMN1), cystic fibrosis transmembrane conductance regulator (CFTR) and DMD proteins...
May 28, 2018: Biosensors & Bioelectronics
Susana Brun, Nicolas Schall, Srinivasa Reddy Bonam, Kévin Bigaut, Ayikoe-Guy Mensah-Nyagan, Jérôme de Sèze, Sylviane Muller
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an autoimmune disease of the peripheral nerves evolving with diffuse sensory and motor symptoms. Although it is claimed that in neurodegenerative pathologies, a common feature is the failure of proteolytic systems to adequately eliminate aggregated or misfolded proteins, it has not been addressed whether autophagy, a central "clearance" system delivering damaged intracellular components to lysosomes, is affected in CIDP. The focus of the present investigation was therefore to determine if some defects exist in autophagy processes in this setting and if they can be corrected or minimized using an appropriate treatment targeting this survival pathway...
June 5, 2018: Journal of Autoimmunity
Florian Krach, Ranjan Batra, Emily C Wheeler, Anthony Q Vu, Ruth Wang, Kasey Hutt, Stuart J Rabin, Michael W Baughn, Ryan T Libby, Sandra Diaz-Garcia, Jennifer Stauffer, Elaine Pirie, Shahram Saberi, Maria Rodriguez, Assael A Madrigal, Zacharias Kohl, Beate Winner, Gene W Yeo, John Ravits
Sporadic amyotrophic lateral sclerosis (sALS) is the most common form of ALS, however, the molecular mechanisms underlying cellular damage and motor neuron degeneration remain elusive. To identify molecular signatures of sALS we performed genome-wide expression profiling in laser capture microdissection-enriched surviving motor neurons (MNs) from lumbar spinal cords of sALS patients with rostral onset and caudal progression. After correcting for immunological background, we discover a highly specific gene expression signature for sALS that is associated with phosphorylated TDP-43 (pTDP-43) pathology...
June 7, 2018: Acta Neuropathologica
Daria Guseva, Igor Jakovcevski, Andrey Irintchev, Iryna Leshchyns'ka, Vladimir Sytnyk, Evgeni Ponimaskin, Melitta Schachner
The close homolog of L1 (CHL1) is a cell adhesion molecule involved in regulation of neuronal differentiation and survival, neurite outgrowth and axon guidance during development. In the mature nervous system, CHL1 regulates synaptic activity and plasticity. The aim of the present study was to evaluate the influence of CHL1 on peripheral nerve regeneration after trauma. Using the established model of mouse femoral nerve regeneration, CHL1 knock-out mice were investigated in comparison to the wild type littermates...
2018: Frontiers in Molecular Neuroscience
Ronglin Wang, Fangfang Lu, Gang Zhu, Dayun Feng, Tiejian Nie, Kai Tao, Shaosong Yang, Jie Lei, Lu Huang, Zixu Mao, Qian Yang
MiRNAs, a group of powerful modulator of gene expression, participate in multiple cellular processes under physiological and pathological conditions. Emerging evidence shows that Drosha, which controls the initial step in canonical miRNA biogenesis, is involved in modulating cell survival and death in models of several diseases. However, the role of Drosha in Parkinson's disease (PD) has not been well established. Here, we show that the level of Drosha decreases in 6-OHDA-induced cellular and animal models of PD...
June 7, 2018: Cell Death & Disease
Jong Hee Choi, Minhee Jang, Seikwan Oh, Seung-Yeol Nah, Ik-Hyun Cho
Gintonin is a ginseng-derived lysophosphatidic acid receptor (LPAR) ligand. Although previous in vitro and in vivo studies demonstrated the therapeutic role of gintonin against Alzheimer's disease, the neuroprotective effects of gintonin in Parkinson's disease (PD) are still unknown. We investigated whether gintonin (50 and 100 mg/kg/day, p.o., daily for 12 days) had neuroprotective activities against neurotoxicity in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. Pre-administration of 100 mg/kg gintonin displayed significantly ameliorating effects in neurological disorders (motor and welfare) as measuring using pole, rotarod, and nest building tests, and in the survival rate...
2018: Frontiers in Pharmacology
Lyandysha Viktorovna Zholudeva, Nisha R Iyer, Liang Qiang, Victoria Marie Spruance, Margo L Randelman, Nicholas W White, Tatiana Bezdudnaya, Itzhak Fischer, Shelly E Sakiyama-Elbert, Michael A Lane
There is growing interest in the use of neural precursor cells to treat spinal cord injury (SCI). Despite extensive preclinical research, it remains unclear as to i) which donor neuron phenotypes are available for transplantation, ii) whether the same populations exist across different sources of donor tissue (e.g. developing tissue vs cultured cells), and iii) whether donor cells retain their phenotype once transplanted into the hostile internal milieu of the injured adult spinal cord. In addition, while functional improvements have been reported after neural precursor transplantation post-SCI, the extent of recovery is limited and variable...
June 6, 2018: Journal of Neurotrauma
Helena Chaytow, Yu-Ting Huang, Thomas H Gillingwater, Kiterie M E Faller
Ever since loss of survival motor neuron (SMN) protein was identified as the direct cause of the childhood inherited neurodegenerative disorder spinal muscular atrophy, significant efforts have been made to reveal the molecular functions of this ubiquitously expressed protein. Resulting research demonstrated that SMN plays important roles in multiple fundamental cellular homeostatic pathways, including a well-characterised role in the assembly of the spliceosome and biogenesis of ribonucleoproteins. More recent studies have shown that SMN is also involved in other housekeeping processes, including mRNA trafficking and local translation, cytoskeletal dynamics, endocytosis and autophagy...
June 5, 2018: Cellular and Molecular Life Sciences: CMLS
Michal Izrael, Shalom Guy Slutsky, Tamar Admoni, Louisa Cohen, Avital Granit, Arik Hasson, Joseph Itskovitz-Eldor, Lena Krush Paker, Graciela Kuperstein, Neta Lavon, Shiran Yehezkel Ionescu, Leonardo Javier Solmesky, Rachel Zaguri, Alina Zhuravlev, Ella Volman, Judith Chebath, Michel Revel
BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a motor neuron (MN) disease characterized by the loss of MNs in the central nervous system. As MNs die, patients progressively lose their ability to control voluntary movements, become paralyzed and eventually die from respiratory/deglutition failure. Despite the selective MN death in ALS, there is growing evidence that malfunctional astrocytes play a crucial role in disease progression. Thus, transplantation of healthy astrocytes may compensate for the diseased astrocytes...
June 6, 2018: Stem Cell Research & Therapy
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