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Axonal neuropathy

Adam DeBusk, Mark L Moster
PURPOSE OF REVIEW: Highlight some of the recent advances in gene therapy and gene modification for optic nerve disease to promote axon regeneration, neuroprotection, and increased visual functioning. RECENT FINDINGS: Visual loss secondary to optic nerve damage occurs in numerous ophthalmologic and neurologic conditions. Damaged retinal ganglion cells (RGCs) do not regenerate once they undergo apoptosis after injury. Gene therapy has been studied to replace gene mutations in disorders affecting the optic nerve as well as to alter genes responsible for suppressing or activating pathways of optic nerve growth and regeneration...
March 13, 2018: Current Opinion in Ophthalmology
Shandiz Tehrani, R Katherine Delf, William O Cepurna, Lauren Davis, Elaine C Johnson, John C Morrison
Small molecule delivery to the optic nerve would allow for exploration of molecular and cellular pathways involved in normal physiology and optic neuropathies such as glaucoma, and provide a tool for screening therapeutics in animal models. We report a novel surgical method for small molecule drug delivery to the optic nerve head (ONH) in a rodent model. In proof-of-principle experiments, we delivered cytochalasin D (Cyt D; a filamentous actin inhibitor) to the junction of the superior optic nerve and globe in rats to target the actin-rich astrocytic cytoskeleton of the ONH...
March 13, 2018: Scientific Reports
Nirupa D Jayaraj, Bula J Bhattacharyya, Abdelhak A Belmadani, Dongjun Ren, Craig A Rathwell, Sandra Hackelberg, Brittany E Hopkins, Herschel R Gupta, Richard J Miller, Daniela M Menichella
Painful diabetic neuropathy (PDN) is an intractable complication of diabetes that affects 25% of patients. PDN is characterized by neuropathic pain and small-fiber degeneration, accompanied by dorsal root ganglion (DRG) nociceptor hyperexcitability and loss of their axons within the skin. The molecular mechanisms underlying DRG nociceptor hyperexcitability and small-fiber degeneration in PDN are unknown. We hypothesize that chemokine CXCL12/CXCR4 signaling is central to this mechanism, as we have shown that CXCL12/CXCR4 signaling is necessary for the development of mechanical allodynia, a pain hypersensitivity behavior common in PDN...
March 13, 2018: Journal of Clinical Investigation
Peter Chung, Hope Northrup, Misbah Azmath, Ricardo A Mosquera, Shade Moody, Aravind Yadav
Distal hereditary motor neuropathies (dHMN) are a rare heterogeneous group of inherited disorders specifically affecting the motor axons, leading to distal limb neurogenic muscular atrophy. The GARS gene has been identified as a causative gene responsible for clinical features of dHMN type V in families from different ethnic origins and backgrounds. We present the first cohort of family members of Nigerian descent with a novel heterozygous p.L272R variant on the GARS gene. We postulate that this variant is the cause of dHMN-V in this family, leading to variable phenotypical expressions that are earlier than reported in previous cases...
2018: Case Reports in Pediatrics
Kimberly A Fernandes, Katherine L Mitchell, Amit Patel, Olivia J Marola, Peter Shrager, Donald J Zack, Richard T Libby, Derek S Welsbie
Optic neuropathies such as glaucoma are characterized by the degeneration of retinal ganglion cells (RGCs) and the irreversible loss of vision. In these diseases, focal axon injury triggers a propagating axon degeneration and, eventually, cell death. Previous work by us and others identified dual leucine zipper kinase (DLK) and JUN N-terminal kinase (JNK) as key mediators of somal cell death signaling in RGCs following axonal injury. Moreover, others have shown that activation of the DLK/JNK pathway contributes to distal axonal degeneration in some neuronal subtypes and that this activation is dependent on the adaptor protein, sterile alpha and TIR motif containing 1 (SARM1)...
March 8, 2018: Experimental Eye Research
Brigitte Tampin, Jan Vollert, Annina B Schmid
OBJECTIVE: Distal and proximal entrapment neuropathies such as carpal tunnel syndrome (CTS) and cervical radiculopathy (CR) share similar etiologies. Experimental models suggest that despite comparable etiology, pathomechanisms associated with injuries of the peripheral and central axon branches are distinct. This study therefore compared self-reported and elicited sensory profiles in patients with distal and proximal entrapment neuropathies. METHODS: Patients with electrodiagnostically confirmed CTS (n = 103) and patients with CR (n = 23) were included in this study...
March 10, 2018: Current Medical Research and Opinion
Giulia Coarelli, Silvia Romano, Lorena Travaglini, Michela Ferraldeschi, Francesco Nicita, Maria Spadaro, Arianna Fornasiero, Marina Frontali, Marco Salvetti, Enrico Bertini, Giovanni Ristori
Hereditary spastic paraplegias (HSPs) are a heterogeneous group of neurological disorders characterized primarily by a pyramidal syndrome with lower limb spasticity, which can manifest as pure HSP or associated with a number of neurological or non-neurological signs (i.e., complicated HSPs). The clinical variability of HSPs is associated with a wide genetic heterogeneity, with more than eighty causative genes known. Recently, next generation sequencing (NGS) has allowed increasing genetic definition in such a heterogeneous group of disorders...
March 3, 2018: Clinical Neurology and Neurosurgery
Broes Martens, Michel De Pauw, Jan L De Bleecker
Familial amyloid polyneuropathy (FAP) is a most often length-dependent axonal neuropathy, often part of a multisystem disorder also affecting other organs, such as cardiac, gastrointestinal, genitourinary, renal, meningeal and eye tissue. It is most frequently the result of a mutation in the TTR gene, most commonly a p.Val50Met mutation. TTR-FAP is a rare autosomal dominant heritable disabling, heterogeneous disease in which early diagnosis is of pivotal importance when attempting treatment. This paper discusses the course of four Belgian FAP patients with different TTR mutations (p...
March 9, 2018: Acta Neurologica Belgica
Hok Khim Fam, Kunho Choi, Lauren Fougner, Chinten James Lim, Cornelius F Boerkoel
Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a nuclear and mitochondrial protein that in nuclei and in vitro repairs blocked 3' DNA termini such as 3' phosphotyrosine conjugates resulting from stalling of topoisomerase I-DNA intermediates. Its mutation also causes spinocerebellar ataxia with axonal neuropathy type 1 (SCAN1). Because Tdp1 colocalizes with mitochondria following oxidative stress, we hypothesized that Tdp1 repairs mitochondrial DNA (mtDNA) and that mtDNA damage mediates entry of Tdp1 into the mitochondria...
March 9, 2018: Scientific Reports
Stuart J Grice, James N Sleigh, M Zameel Cader
Dominant mutations in GARS , encoding the ubiquitous enzyme glycyl-tRNA synthetase (GlyRS), cause peripheral nerve degeneration and Charcot-Marie-Tooth disease type 2D (CMT2D). This genetic disorder exemplifies a recurring paradigm in neurodegeneration, in which mutations in essential genes cause selective degeneration of the nervous system. Recent evidence suggests that the mechanism underlying CMT2D involves extracellular neomorphic binding of mutant GlyRS to neuronally-expressed proteins. Consistent with this, our previous studies indicate a non-cell autonomous mechanism, whereby mutant GlyRS is secreted and interacts with the neuromuscular junction (NMJ)...
2018: Frontiers in Molecular Neuroscience
Zhongying Mo, Xiaobei Zhao, Huaqing Liu, Qinghua Hu, Xu-Qiao Chen, Jessica Pham, Na Wei, Ze Liu, Jiadong Zhou, Robert W Burgess, Samuel L Pfaff, C Thomas Caskey, Chengbiao Wu, Ge Bai, Xiang-Lei Yang
Dominant mutations in glycyl-tRNA synthetase (GlyRS) cause a subtype of Charcot-Marie-Tooth neuropathy (CMT2D). Although previous studies have shown that GlyRS mutants aberrantly interact with Nrp1, giving insight into the disease's specific effects on motor neurons, these cannot explain length-dependent axonal degeneration. Here, we report that GlyRS mutants interact aberrantly with HDAC6 and stimulate its deacetylase activity on α-tubulin. A decrease in α-tubulin acetylation and deficits in axonal transport are observed in mice peripheral nerves prior to disease onset...
March 8, 2018: Nature Communications
Laura R Rich, Angus M Brown
The stimulus evoked compound action potential (CAP), recorded using suction electrodes, provides an index of the relative number of conducting axons within a nerve trunk. As such the CAP has been used to elucidate the diverse mechanisms of injury resulting from a variety of metabolic insults to central nervous white matter, whilst also providing a model with which to assess the benefits of clinically relevant neuro-protective strategies. In addition the technique lends itself to the study of metabolic cell-to-cell signalling that occurs between glial cells and neurones, and to exploring the ability of non-glucose substrates to support axon conduction...
March 8, 2018: Journal of Physiology
Lu-Mei Chi, Yu Gao, Guang-Xian Nan
RATIONALE: Neuromyelitis optica spectrum disorders (NMOSDs) represent recurrent autoimmune diseases, generally beginning with optic nerve neuritis or acute transverse myelitis. PATIENT CONCERNS: A 57-year-old male with long-term alcohol intake was hospitalized because of limb numbness. EMG examination showed the peripheral sensory nerve was in demyelination and an axonal injury was found. His symptoms could not be improved by vitamin B injection but were later significantly attenuated by dexamethasone treatment...
March 2018: Medicine (Baltimore)
Maria Veronica Strehaianu, Dana Dascalescu, Catalina Ionescu, Miruna Burcel, Vasile Potop, Catalina Corbu
Glaucoma is an optic neuropathy that affects the ganglion cell complex in all its components: cell bodies, dendrites, and axons, the dendritic arbor being the first one damaged. This is the reason why the thickness of the ganglion cell and internal plexiform layers can be taken into account as an early predictor of the glaucomatous changes, along with the retinal nerve fiber layer (RNFL) thickness. However, due to disc tilting and peripapillary atrophy, the RNFL evaluation may be prone to errors in myopic patients...
October 2017: Romanian Journal of Ophthalmology
Rola A Mahmoud, Charles K Abrams
Peripheral neurological complications of lymphomas are rare and much less frequent than central complications. Nonetheless, on occasion, systemic non-Hodgkin's lymphoma may directly infiltrate the peripheral nervous system at various levels. This report describes a man with non-Hodgkin's lymphoma and leptomeningeal disease who developed progressive areflexic quadraparesis. Initial electromyography (EMG) was consistent with a polyradiculopathy and a repeat EMG performed 1 month later for worsening symptoms showed evidence of demyelination...
March 5, 2018: BMJ Case Reports
Ioannis Karakis, Sofia Georghiou, H Royden Jones, Basil T Darras, Peter B Kang
BACKGROUND: We analyzed the clinical and electrophysiologic patterns of nerve injury in pediatric patients with radial neuropathy. METHODS: This is a retrospective analysis of 19 children and adolescents with radial neuropathy. RESULTS: The mean subject age was 12 years (range one month to 19 years), 56% were female, and 53% had traumatic etiologies. Weakness in the finger and wrist extensors was the prevailing complaint (82%). Predominant localization was at the posterior interosseous nerve (37%), followed by the radial nerve below the spiral groove (32%), the radial nerve at the spiral groove (26%), and the radial nerve above the spiral groove (5%)...
January 31, 2018: Pediatric Neurology
Vuu My Dung, Dang Ngoc Anh Suong, Yuji Okamaoto, Yu Hiramatsu, Dang Thi Phuong Thao, Hideki Yoshida, Hiroshi Takashima, Masamitsu Yamaguchi
Pyruvate dehydrogenase complex deficiency (PDCD) is a common primary cause of defects in mitochondrial function and also can lead to peripheral neuropathy. Pyruvate dehydrogenase E1 component subunit beta (PDHB) is a subunit of pyruvate dehydrogenase E1, which is a well-known component of PDC. In Drosophila melanogaster, the CG11876 (dPDHB) gene is a homolog of human PDHB. In this study, we established a Drosophila model with neuron-specific knockdown of dPDHB to investigate its role in neuropathy pathogenesis...
February 28, 2018: Experimental Cell Research
Nathalie Bernard-Marissal, Roman Chrast, Bernard L Schneider
Recent progress in the understanding of neurodegenerative diseases revealed that multiple molecular mechanisms contribute to pathological changes in neurons. A large fraction of these alterations can be linked to dysfunction in the endoplasmic reticulum (ER) and mitochondria, affecting metabolism and secretion of lipids and proteins, calcium homeostasis, and energy production. Remarkably, these organelles are interacting with each other at specialized domains on the ER called mitochondria-associated membranes (MAMs)...
February 28, 2018: Cell Death & Disease
Cameron Green, Tess Baker, Ashwin Subramaniam
OBJECTIVE: To systematically review the literature regarding the ability of clinical features to predict respiratory failure in patients with Guillain-Barré syndrome (GBS). DATA SOURCES: We searched the PubMed and Ovid MEDLINE databases with the search terms "guillain barre syndrome" OR "acute inflammatory demyelinating polyneuropathy" OR "acute motor axonal neuropathy" OR "acute motor sensory axonal neuropathy" AND "respiratory failure" OR "mechanical ventilation"...
March 5, 2018: Medical Journal of Australia
Kei-Ichi Nakashima, Keiichiro Iwao, Toshihiro Inoue, Akira Haga, Takayuki Tsutsumi, Miyuki Inoue Mochita, Tomokazu Fujimoto, Hidenobu Tanihara
Among candidate neuroprotective agents, adenosine is thought to be a possible treatment for central nervous system disorders. Adenosine elicits biological effects through four G protein-coupled receptors (A1 , A2A , A2B , and A3 ). The A2A and A2B receptors stimulate adenylyl cyclase (AC) and increase cyclic adenosine monophosphate (cAMP) levels, whereas A1 and A3 receptors inhibit AC and decrease cAMP levels. Several studies have investigated the effects of adenosine receptors (AdoRs) in glaucoma, because modulation of A1 , A2A , or A3 receptor regulates intraocular pressure...
February 24, 2018: Experimental Eye Research
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