PMID- 10649571
OWN - NLM
STAT- MEDLINE
DCOM- 20000407
LR  - 20191210
IS  - 1097-6256 (Print)
IS  - 1097-6256 (Linking)
VI  - 3
IP  - 2
DP  - 2000 Feb
TI  - Polyglutamine expansion down-regulates specific neuronal genes before pathologic 
      changes in SCA1.
PG  - 157-63
AB  - The expansion of an unstable CAG repeat causes spinocerebellar ataxia type 1
      (SCA1) and several other neurodegenerative diseases. How polyglutamine expansions
      render the resulting proteins toxic to neurons, however, remains elusive.
      Hypothesizing that long polyglutamine tracts alter gene expression, we found
      certain neuronal genes involved in signal transduction and calcium homeostasis
      sequentially downregulated in SCA1 mice. These genes were abundant in Purkinje
      cells, the primary site of SCA1 pathogenesis; moreover, their downregulation was 
      mediated by expanded ataxin-1 and occurred before detectable pathology. Similar
      downregulation occurred in SCA1 human tissues. Altered gene expression may be the
      earliest mediator of polyglutamine toxicity.
FAU - Lin, X
AU  - Lin X
AD  - Howard Hughes Medical Institute, Baylor College of Medicine, One Baylor Plaza,
      Houston, Texas 77030, USA.
FAU - Antalffy, B
AU  - Antalffy B
FAU - Kang, D
AU  - Kang D
FAU - Orr, H T
AU  - Orr HT
FAU - Zoghbi, H Y
AU  - Zoghbi HY
LA  - eng
GR  - NS22920/NS/NINDS NIH HHS/United States
GR  - NS27699/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Nat Neurosci
JT  - Nature neuroscience
JID - 9809671
RN  - 0 (ATXN1 protein, human)
RN  - 0 (Amino Acid Transport System X-AG)
RN  - 0 (Ataxin-1)
RN  - 0 (Ataxins)
RN  - 0 (Atxn1 protein, mouse)
RN  - 0 (Calcium Channels)
RN  - 0 (Glutamate Plasma Membrane Transport Proteins)
RN  - 0 (ITPR1 protein, human)
RN  - 0 (Inositol 1,4,5-Trisphosphate Receptors)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Peptides)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Receptors, Glutamate)
RN  - 0 (Symporters)
RN  - 0 (TRPC Cation Channels)
RN  - 0 (alpha 1-Antichymotrypsin)
RN  - 0 (transient receptor potential cation channel, subfamily C, member 1)
RN  - 26700-71-0 (polyglutamine)
RN  - EC 2.1.1.- (Protein Methyltransferases)
RN  - EC 2.1.1.100 (protein-S-isoprenylcysteine O-methyltransferase)
RN  - EC 3.1.3.2 (Phosphoric Monoester Hydrolases)
RN  - EC 3.1.3.56 (Inositol Polyphosphate 5-Phosphatases)
RN  - EC 7.2.2.10 (Calcium-Transporting ATPases)
SB  - IM
CIN - Nat Neurosci. 2000 Feb;3(2):103-4. PMID: 10649562
MH  - *Amino Acid Transport System X-AG
MH  - Animals
MH  - Ataxin-1
MH  - Ataxins
MH  - Brain/enzymology
MH  - Calcium Channels/metabolism
MH  - Calcium-Transporting ATPases/metabolism
MH  - Cloning, Molecular
MH  - Disease Models, Animal
MH  - Down-Regulation/*genetics
MH  - Gene Expression Regulation
MH  - Glutamate Plasma Membrane Transport Proteins
MH  - Humans
MH  - Inositol 1,4,5-Trisphosphate Receptors
MH  - Inositol Polyphosphate 5-Phosphatases
MH  - Mice
MH  - Mice, Transgenic
MH  - Molecular Sequence Data
MH  - Nerve Tissue Proteins
MH  - Neurons/*enzymology
MH  - Nuclear Proteins
MH  - Organ Specificity
MH  - Peptides/*genetics
MH  - Phosphoric Monoester Hydrolases/metabolism
MH  - Protein Methyltransferases/biosynthesis/chemistry/genetics
MH  - Purkinje Cells/enzymology
MH  - RNA, Messenger/biosynthesis
MH  - Receptors, Cytoplasmic and Nuclear/metabolism
MH  - Receptors, Glutamate/metabolism
MH  - Signal Transduction/genetics
MH  - Spinocerebellar Ataxias/etiology/*genetics/metabolism
MH  - *Symporters
MH  - TRPC Cation Channels
MH  - Trinucleotide Repeat Expansion/*genetics
MH  - alpha 1-Antichymotrypsin/metabolism
EDAT- 2000/01/29 09:00
MHDA- 2001/03/23 10:01
CRDT- 2000/01/29 09:00
PHST- 2000/01/29 09:00 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 2000/01/29 09:00 [entrez]
AID - 10.1038/72101 [doi]
PST - ppublish
SO  - Nat Neurosci. 2000 Feb;3(2):157-63. doi: 10.1038/72101.