Early and selective reduction of NOP56 (Asidan) and RNA processing proteins in the motor neuron of ALS model mice

Kazunori Miyazaki, Toru Yamashita, Nobutoshi Morimoto, Kota Sato, Takafumi Mimoto, Tomoko Kurata, Yoshio Ikeda, Koji Abe

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Objective: There is increasing evidence to support that altered RNA processing is implicated in the pathogenesis of motor neuron degeneration of amyotrophic lateral sclerosis (ALS). We evaluate the expression of three RNA processing-related proteins in ALS model mice in this study. Methods: We analyzed expression and distribution patterns of three RNA processing-related proteins, nucleolar protein (NOP) 56 (identified as causative gene for spinocerebellar ataxia (SCA) 36, nicknamed Asidan), TDP-43, and fused in sarcoma/translocated in liposarcoma (FUS) in lumbar and cervical cords, hypoglossal nucleus, cerebral motor cortex, and cerebellum of transgenic (Tg) SOD1 G93A ALS model mice throughout the course of motor neuron degeneration. Results: Compared to age-matched wild type (WT) mice, Tg mice showed progressive reduction of NOP56 levels in the large motor neurons of lumbar and cervical cords from the early-symptomatic stage (14 weeks of age) to the end stage of the disease (18 weeks). TDP-43 and FUS protein levels showed a later decrease in the nucleus of large motor neuron at 18 weeks (end stage of the disease). These changes were not observed in the primary motor cortex of the cerebrum as well as molecular and granular layers and Purkinje cells in the cerebellum. Discussion: The present study suggests a progressive loss of these three nuclear proteins and subsequent RNA processing problems including a novel gene relating to ALS (NOP56) under the motor neuron degeneration.

Original languageEnglish
Pages (from-to)744-754
Number of pages11
JournalNeurological Research
Volume35
Issue number7
DOIs
Publication statusPublished - Sep 2013

Fingerprint

Amyotrophic Lateral Sclerosis
Motor Neurons
Nerve Degeneration
RNA
Motor Cortex
Nuclear Proteins
Proteins
Cerebellum
RNA-Binding Protein FUS
Spinal Cord
Spinocerebellar Ataxias
Liposarcoma
Purkinje Cells
Cerebrum
Sarcoma
Cerebral Cortex
Transgenic Mice
Genes
Cervical Cord

Keywords

  • Asidan
  • Cu/zn-superoxide dismutase 1 (SOD1) G93A
  • Fused in sarcoma/translocated in liposarcoma (FUS)
  • Nucleolar protein (NOP) 56
  • TAR DNA binding protein-43 (TDP-43)

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

Early and selective reduction of NOP56 (Asidan) and RNA processing proteins in the motor neuron of ALS model mice. / Miyazaki, Kazunori; Yamashita, Toru; Morimoto, Nobutoshi; Sato, Kota; Mimoto, Takafumi; Kurata, Tomoko; Ikeda, Yoshio; Abe, Koji.

In: Neurological Research, Vol. 35, No. 7, 09.2013, p. 744-754.

Research output: Contribution to journalArticle

Miyazaki, Kazunori ; Yamashita, Toru ; Morimoto, Nobutoshi ; Sato, Kota ; Mimoto, Takafumi ; Kurata, Tomoko ; Ikeda, Yoshio ; Abe, Koji. / Early and selective reduction of NOP56 (Asidan) and RNA processing proteins in the motor neuron of ALS model mice. In: Neurological Research. 2013 ; Vol. 35, No. 7. pp. 744-754.
@article{4086316971da4bf4912b96d1d57a3cc4,
title = "Early and selective reduction of NOP56 (Asidan) and RNA processing proteins in the motor neuron of ALS model mice",
abstract = "Objective: There is increasing evidence to support that altered RNA processing is implicated in the pathogenesis of motor neuron degeneration of amyotrophic lateral sclerosis (ALS). We evaluate the expression of three RNA processing-related proteins in ALS model mice in this study. Methods: We analyzed expression and distribution patterns of three RNA processing-related proteins, nucleolar protein (NOP) 56 (identified as causative gene for spinocerebellar ataxia (SCA) 36, nicknamed Asidan), TDP-43, and fused in sarcoma/translocated in liposarcoma (FUS) in lumbar and cervical cords, hypoglossal nucleus, cerebral motor cortex, and cerebellum of transgenic (Tg) SOD1 G93A ALS model mice throughout the course of motor neuron degeneration. Results: Compared to age-matched wild type (WT) mice, Tg mice showed progressive reduction of NOP56 levels in the large motor neurons of lumbar and cervical cords from the early-symptomatic stage (14 weeks of age) to the end stage of the disease (18 weeks). TDP-43 and FUS protein levels showed a later decrease in the nucleus of large motor neuron at 18 weeks (end stage of the disease). These changes were not observed in the primary motor cortex of the cerebrum as well as molecular and granular layers and Purkinje cells in the cerebellum. Discussion: The present study suggests a progressive loss of these three nuclear proteins and subsequent RNA processing problems including a novel gene relating to ALS (NOP56) under the motor neuron degeneration.",
keywords = "Asidan, Cu/zn-superoxide dismutase 1 (SOD1) G93A, Fused in sarcoma/translocated in liposarcoma (FUS), Nucleolar protein (NOP) 56, TAR DNA binding protein-43 (TDP-43)",
author = "Kazunori Miyazaki and Toru Yamashita and Nobutoshi Morimoto and Kota Sato and Takafumi Mimoto and Tomoko Kurata and Yoshio Ikeda and Koji Abe",
year = "2013",
month = "9",
doi = "10.1179/1743132813Y.0000000196",
language = "English",
volume = "35",
pages = "744--754",
journal = "Neurological Research",
issn = "0161-6412",
publisher = "Maney Publishing",
number = "7",

}

TY - JOUR

T1 - Early and selective reduction of NOP56 (Asidan) and RNA processing proteins in the motor neuron of ALS model mice

AU - Miyazaki, Kazunori

AU - Yamashita, Toru

AU - Morimoto, Nobutoshi

AU - Sato, Kota

AU - Mimoto, Takafumi

AU - Kurata, Tomoko

AU - Ikeda, Yoshio

AU - Abe, Koji

PY - 2013/9

Y1 - 2013/9

N2 - Objective: There is increasing evidence to support that altered RNA processing is implicated in the pathogenesis of motor neuron degeneration of amyotrophic lateral sclerosis (ALS). We evaluate the expression of three RNA processing-related proteins in ALS model mice in this study. Methods: We analyzed expression and distribution patterns of three RNA processing-related proteins, nucleolar protein (NOP) 56 (identified as causative gene for spinocerebellar ataxia (SCA) 36, nicknamed Asidan), TDP-43, and fused in sarcoma/translocated in liposarcoma (FUS) in lumbar and cervical cords, hypoglossal nucleus, cerebral motor cortex, and cerebellum of transgenic (Tg) SOD1 G93A ALS model mice throughout the course of motor neuron degeneration. Results: Compared to age-matched wild type (WT) mice, Tg mice showed progressive reduction of NOP56 levels in the large motor neurons of lumbar and cervical cords from the early-symptomatic stage (14 weeks of age) to the end stage of the disease (18 weeks). TDP-43 and FUS protein levels showed a later decrease in the nucleus of large motor neuron at 18 weeks (end stage of the disease). These changes were not observed in the primary motor cortex of the cerebrum as well as molecular and granular layers and Purkinje cells in the cerebellum. Discussion: The present study suggests a progressive loss of these three nuclear proteins and subsequent RNA processing problems including a novel gene relating to ALS (NOP56) under the motor neuron degeneration.

AB - Objective: There is increasing evidence to support that altered RNA processing is implicated in the pathogenesis of motor neuron degeneration of amyotrophic lateral sclerosis (ALS). We evaluate the expression of three RNA processing-related proteins in ALS model mice in this study. Methods: We analyzed expression and distribution patterns of three RNA processing-related proteins, nucleolar protein (NOP) 56 (identified as causative gene for spinocerebellar ataxia (SCA) 36, nicknamed Asidan), TDP-43, and fused in sarcoma/translocated in liposarcoma (FUS) in lumbar and cervical cords, hypoglossal nucleus, cerebral motor cortex, and cerebellum of transgenic (Tg) SOD1 G93A ALS model mice throughout the course of motor neuron degeneration. Results: Compared to age-matched wild type (WT) mice, Tg mice showed progressive reduction of NOP56 levels in the large motor neurons of lumbar and cervical cords from the early-symptomatic stage (14 weeks of age) to the end stage of the disease (18 weeks). TDP-43 and FUS protein levels showed a later decrease in the nucleus of large motor neuron at 18 weeks (end stage of the disease). These changes were not observed in the primary motor cortex of the cerebrum as well as molecular and granular layers and Purkinje cells in the cerebellum. Discussion: The present study suggests a progressive loss of these three nuclear proteins and subsequent RNA processing problems including a novel gene relating to ALS (NOP56) under the motor neuron degeneration.

KW - Asidan

KW - Cu/zn-superoxide dismutase 1 (SOD1) G93A

KW - Fused in sarcoma/translocated in liposarcoma (FUS)

KW - Nucleolar protein (NOP) 56

KW - TAR DNA binding protein-43 (TDP-43)

UR - http://www.scopus.com/inward/record.url?scp=84882646616&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84882646616&partnerID=8YFLogxK

U2 - 10.1179/1743132813Y.0000000196

DO - 10.1179/1743132813Y.0000000196

M3 - Article

C2 - 23582672

AN - SCOPUS:84882646616

VL - 35

SP - 744

EP - 754

JO - Neurological Research

JF - Neurological Research

SN - 0161-6412

IS - 7

ER -