PMID- 21228155
OWN - NLM
STAT- MEDLINE
DCOM- 20110222
LR  - 20211203
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 31
IP  - 2
DP  - 2011 Jan 12
TI  - Nucleolar disruption in dopaminergic neurons leads to oxidative damage and 
      parkinsonism through repression of mammalian target of rapamycin signaling.
PG  - 453-60
LID - 10.1523/JNEUROSCI.0590-10.2011 [doi]
AB  - The nucleolus represents an essential stress sensor for the cell. However, the 
      molecular consequences of nucleolar damage and their possible link with 
      neurodegenerative diseases remain to be elucidated. Here, we show that nucleolar 
      damage is present in both genders in Parkinson's disease (PD) and in the 
      pharmacological PD model induced by the neurotoxin 
      1,2,3,6-tetrahydro-1-methyl-4-phenylpyridine hydrochloride (MPTP). Mouse mutants 
      with nucleolar disruption restricted to dopaminergic (DA) neurons show phenotypic 
      alterations that resemble PD, such as progressive and differential loss of DA 
      neurons and locomotor abnormalities. At the molecular level, nucleolar disruption 
      results in increased p53 levels and downregulation of mammalian target of 
      rapamycin (mTOR) activity, leading to mitochondrial dysfunction and increased 
      oxidative stress, similar to PD. In turn, increased oxidative stress induced by 
      MPTP causes mTOR and ribosomal RNA synthesis inhibition. Collectively, these 
      observations suggest that the interplay between nucleolar dysfunction and 
      increased oxidative stress, involving p53 and mTOR signaling, may constitute a 
      destructive axis in experimental and sporadic PD.
FAU - Rieker, Claus
AU  - Rieker C
AD  - Division of Molecular Biology of the Cell I, German Cancer Research Center, 
      Heidelberg, Germany.
FAU - Engblom, David
AU  - Engblom D
FAU - Kreiner, Grzegorz
AU  - Kreiner G
FAU - Domanskyi, Andrii
AU  - Domanskyi A
FAU - Schober, Andreas
AU  - Schober A
FAU - Stotz, Stefanie
AU  - Stotz S
FAU - Neumann, Manuela
AU  - Neumann M
FAU - Yuan, Xuejun
AU  - Yuan X
FAU - Grummt, Ingrid
AU  - Grummt I
FAU - Schutz, Gunther
AU  - Schutz G
FAU - Parlato, Rosanna
AU  - Parlato R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Pol1 Transcription Initiation Complex Proteins)
RN  - 0 (Rrn3 protein, mouse)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 9P21XSP91P (1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
MH  - Animals
MH  - Brain/metabolism/pathology
MH  - Cell Nucleolus/metabolism/*pathology
MH  - Dopamine/*metabolism
MH  - Gene Deletion
MH  - Humans
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Mutant Strains
MH  - Mice, Transgenic
MH  - Mitochondria/physiology
MH  - Motor Skills
MH  - Neurons/metabolism/*pathology
MH  - *Oxidative Stress
MH  - Parkinson Disease/pathology
MH  - Parkinsonian Disorders/*metabolism/*pathology/physiopathology
MH  - Pol1 Transcription Initiation Complex Proteins/genetics
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/*physiology
MH  - Tumor Suppressor Protein p53/physiology
PMC - PMC6623444
EDAT- 2011/01/14 06:00
MHDA- 2011/02/23 06:00
PMCR- 2011/07/12
CRDT- 2011/01/14 06:00
PHST- 2011/01/14 06:00 [entrez]
PHST- 2011/01/14 06:00 [pubmed]
PHST- 2011/02/23 06:00 [medline]
PHST- 2011/07/12 00:00 [pmc-release]
AID - 31/2/453 [pii]
AID - 3656649 [pii]
AID - 10.1523/JNEUROSCI.0590-10.2011 [doi]
PST - ppublish
SO  - J Neurosci. 2011 Jan 12;31(2):453-60. doi: 10.1523/JNEUROSCI.0590-10.2011.