The Axon Guidance Protein Semaphorin 3A Is Increased in the Motor Cortex of Patients With Amyotrophic Lateral Sclerosis
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The Axon Guidance Protein Semaphorin 3A Is Increased in the Motor Cortex of Patients With Amyotrophic Lateral Sclerosis. / Körner, Sonja; Böselt, Sebastian; Wichmann, Klaudia; Thau-Habermann, Nadine; Zapf, Antonia; Knippenberg, Sarah; Dengler, Reinhard; Petri, Susanne.
In: J NEUROPATH EXP NEUR, Vol. 75, No. 4, 25.02.2016, p. 326–333.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - The Axon Guidance Protein Semaphorin 3A Is Increased in the Motor Cortex of Patients With Amyotrophic Lateral Sclerosis
AU - Körner, Sonja
AU - Böselt, Sebastian
AU - Wichmann, Klaudia
AU - Thau-Habermann, Nadine
AU - Zapf, Antonia
AU - Knippenberg, Sarah
AU - Dengler, Reinhard
AU - Petri, Susanne
N1 - © 2016 American Association of Neuropathologists, Inc. All rights reserved.
PY - 2016/2/25
Y1 - 2016/2/25
N2 - 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.
AB - 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.
KW - Journal Article
U2 - 10.1093/jnen/nlw003
DO - 10.1093/jnen/nlw003
M3 - SCORING: Journal article
C2 - 26921371
VL - 75
SP - 326
EP - 333
JO - J NEUROPATH EXP NEUR
JF - J NEUROPATH EXP NEUR
SN - 0022-3069
IS - 4
ER -