PMID- 17620987
OWN - NLM
STAT- MEDLINE
DCOM- 20070831
LR  - 20091119
IS  - 0022-3069 (Print)
IS  - 0022-3069 (Linking)
VI  - 66
IP  - 7
DP  - 2007 Jul
TI  - Gene expressions specifically detected in motor neurons (dynactin 1, early growth 
      response 3, acetyl-CoA transporter, death receptor 5, and cyclin C) 
      differentially correlate to pathologic markers in sporadic amyotrophic lateral 
      sclerosis.
PG  - 617-27
AB  - In a differential gene expression profile, we showed previously that dynactin 1 
      (DCTN1), early growth response 3 (EGR3), acetyl-CoA transporter (ACATN), death 
      receptor 5 (DR5), and cyclin C (CCNC) were prominently up- or downregulated in 
      motor neurons of sporadic amyotrophic lateral sclerosis (ALS). In the present 
      study, we examined the correlation between the expression levels of these genes 
      and the levels of pathologic markers for motor neuron degeneration (i.e. 
      cytoplasmic accumulation of phosphorylated neurofilament H [pNF-H] and 
      ubiquitylated protein) and the numbers of residual motor neurons in 20 autopsies 
      of patients with sporadic ALS. DCTN1 and EGR3 were widely downregulated, and the 
      changes in gene expression were correlated to the number of residual motor 
      neurons. In particular, DCTN1 was markedly downregulated in most residual motor 
      neurons before the accumulation of pNF-H, even in cases with well-preserved motor 
      neuron populations. ACATN, DR5, and CCNC were upregulated in subpopulations of 
      residual motor neurons, and their expression levels were well correlated with the 
      levels of pNF-H accumulation and the number of residual motor neurons. The 
      expressions of DCTN1, EGR3, ACATN, and DR5 were all markedly altered before 
      ubiquitylated protein accumulation. DCTN1 downregulation appears to be an early 
      event before the appearance of neurodegeneration markers, whereas upregulations 
      of DR5 and CCNC are relatively later phenomena associated with pathologic markers 
      and leading to neuronal death. The sequence of motor neuron-specific gene 
      expression changes in sporadic ALS can be beneficial information in developing 
      appropriate therapeutic strategies for neurodegeneration.
FAU - Jiang, Yue-Mei
AU  - Jiang YM
AD  - Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, 
      Japan.
FAU - Yamamoto, Masahiko
AU  - Yamamoto M
FAU - Tanaka, Fumiaki
AU  - Tanaka F
FAU - Ishigaki, Shinsuke
AU  - Ishigaki S
FAU - Katsuno, Masahisa
AU  - Katsuno M
FAU - Adachi, Hiroaki
AU  - Adachi H
FAU - Niwa, Jun-Ichi
AU  - Niwa J
FAU - Doyu, Manabu
AU  - Doyu M
FAU - Yoshida, Mari
AU  - Yoshida M
FAU - Hashizume, Yoshio
AU  - Hashizume Y
FAU - Sobue, Gen
AU  - Sobue G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Neuropathol Exp Neurol
JT  - Journal of neuropathology and experimental neurology
JID - 2985192R
RN  - 0 (CCNC protein, human)
RN  - 0 (Cyclin C)
RN  - 0 (Cyclins)
RN  - 0 (EGR3 protein, human)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (Neurofilament Proteins)
RN  - 0 (Receptors, TNF-Related Apoptosis-Inducing Ligand)
RN  - 0 (Ubiquitin)
RN  - 108688-71-7 (neurofilament protein H)
RN  - 144516-98-3 (Early Growth Response Protein 3)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Amyotrophic Lateral Sclerosis/*pathology/*physiopathology
MH  - Cyclin C
MH  - Cyclins/metabolism
MH  - Early Growth Response Protein 3/metabolism
MH  - Female
MH  - Gene Expression Regulation/*physiology
MH  - Humans
MH  - Immunohistochemistry/methods
MH  - In Situ Hybridization/methods
MH  - Male
MH  - Membrane Transport Proteins/metabolism
MH  - Middle Aged
MH  - Motor Neurons/*metabolism
MH  - Neurofilament Proteins/metabolism
MH  - Oligonucleotide Array Sequence Analysis/methods
MH  - Receptors, TNF-Related Apoptosis-Inducing Ligand/metabolism
MH  - Spinal Cord/pathology
MH  - Statistics, Nonparametric
MH  - Ubiquitin/metabolism
EDAT- 2007/07/11 09:00
MHDA- 2007/09/01 09:00
CRDT- 2007/07/11 09:00
PHST- 2007/07/11 09:00 [pubmed]
PHST- 2007/09/01 09:00 [medline]
PHST- 2007/07/11 09:00 [entrez]
AID - 00005072-200707000-00007 [pii]
AID - 10.1097/nen.0b013e318093ece3 [doi]
PST - ppublish
SO  - J Neuropathol Exp Neurol. 2007 Jul;66(7):617-27. doi: 
      10.1097/nen.0b013e318093ece3.