title: The Axon Guidance Protein Semaphorin 3A Is Increased in the Motor Cortex of Patients With Amyotrophic Lateral Sclerosis.
abstract: Amyotrophic lateral sclerosis (ALS) is a degenerative motor neuron disorder that leads to progressive paralysis of skeletal muscles and death by respiratory failure. There is increasing evidence that ALS is at least in part an axonopathy and that mechanisms regulating axonal degeneration and regeneration might be pathogenetically relevant. Semaphorin 3A (Sema3A) is an axon guidance protein; it acts as an axon repellent and prevents axonal regeneration. Increased Sema3A expression has been described in a mouse model of ALS in which it may contribute to motor neuron degeneration. This study aimed to investigate Sema3A mRNA and protein expression in human CNS tissues. We assessed Sema3A expression using quantitative real-time PCR, in situ hybridization, and immunohistochemistry in motor cortex and spinal cord tissue of 8 ALS patients and 6 controls. We found a consistent increase of Sema3A expression in the motor cortex of ALS patients by all 3 methods. In situ hybridization further confirmed that Sema3A expression was present in motor neurons. These findings indicate that upregulation of Sema3A may contribute to axonal degeneration and failure of regeneration in ALS patients. The inhibition of Sema3A therefore might be a promising future therapeutic option for patients with this disease.
authors.affiliation: From the Department of Neurology, Hannover Medical School, Hannover, Germany (SK, SB, KW, NTH, RD); Department of Medical Statistics, University Medical Center, Göttingen, Germany (AZ); Department of Experimental Pneumology, Hannover Medical School, Hannover, Germany (SK); and Center for Systems Neuroscience (ZSN), Hannover, Germany (RD, SP). koerner.sonja@mh-hannover.de.
authors.forename: Sonja
authors.initials: S
authors.lastname: Körner
authors.affiliation: From the Department of Neurology, Hannover Medical School, Hannover, Germany (SK, SB, KW, NTH, RD); Department of Medical Statistics, University Medical Center, Göttingen, Germany (AZ); Department of Experimental Pneumology, Hannover Medical School, Hannover, Germany (SK); and Center for Systems Neuroscience (ZSN), Hannover, Germany (RD, SP).
authors.forename: Sebastian
authors.initials: S
authors.lastname: Böselt
authors.affiliation: From the Department of Neurology, Hannover Medical School, Hannover, Germany (SK, SB, KW, NTH, RD); Department of Medical Statistics, University Medical Center, Göttingen, Germany (AZ); Department of Experimental Pneumology, Hannover Medical School, Hannover, Germany (SK); and Center for Systems Neuroscience (ZSN), Hannover, Germany (RD, SP).
authors.forename: Klaudia
authors.initials: K
authors.lastname: Wichmann
authors.affiliation: From the Department of Neurology, Hannover Medical School, Hannover, Germany (SK, SB, KW, NTH, RD); Department of Medical Statistics, University Medical Center, Göttingen, Germany (AZ); Department of Experimental Pneumology, Hannover Medical School, Hannover, Germany (SK); and Center for Systems Neuroscience (ZSN), Hannover, Germany (RD, SP).
authors.forename: Nadine
authors.initials: N
authors.lastname: Thau-Habermann
authors.affiliation: From the Department of Neurology, Hannover Medical School, Hannover, Germany (SK, SB, KW, NTH, RD); Department of Medical Statistics, University Medical Center, Göttingen, Germany (AZ); Department of Experimental Pneumology, Hannover Medical School, Hannover, Germany (SK); and Center for Systems Neuroscience (ZSN), Hannover, Germany (RD, SP).
authors.forename: Antonia
authors.initials: A
authors.lastname: Zapf
authors.affiliation: From the Department of Neurology, Hannover Medical School, Hannover, Germany (SK, SB, KW, NTH, RD); Department of Medical Statistics, University Medical Center, Göttingen, Germany (AZ); Department of Experimental Pneumology, Hannover Medical School, Hannover, Germany (SK); and Center for Systems Neuroscience (ZSN), Hannover, Germany (RD, SP).
authors.forename: Sarah
authors.initials: S
authors.lastname: Knippenberg
authors.affiliation: From the Department of Neurology, Hannover Medical School, Hannover, Germany (SK, SB, KW, NTH, RD); Department of Medical Statistics, University Medical Center, Göttingen, Germany (AZ); Department of Experimental Pneumology, Hannover Medical School, Hannover, Germany (SK); and Center for Systems Neuroscience (ZSN), Hannover, Germany (RD, SP).
authors.forename: Reinhard
authors.initials: R
authors.lastname: Dengler
authors.affiliation: From the Department of Neurology, Hannover Medical School, Hannover, Germany (SK, SB, KW, NTH, RD); Department of Medical Statistics, University Medical Center, Göttingen, Germany (AZ); Department of Experimental Pneumology, Hannover Medical School, Hannover, Germany (SK); and Center for Systems Neuroscience (ZSN), Hannover, Germany (RD, SP).
authors.forename: Susanne
authors.initials: S
authors.lastname: Petri
keywords: Amyotrophic lateral sclerosis; Anterior horn cell; Axon guidance proteins; In situ hybridization; Motor cortex; Semaphorin 3A.