PMID- 19074039
OWN - NLM
STAT- MEDLINE
DCOM- 20090123
LR  - 20211020
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 28
IP  - 50
DP  - 2008 Dec 10
TI  - Enhanced sensitivity of striatal neurons to axonal transport defects induced by 
      mutant huntingtin.
PG  - 13662-72
LID - 10.1523/JNEUROSCI.4144-08.2008 [doi]
AB  - Huntington's disease (HD) is an autosomal dominant neurodegenerative disease 
      linked to a polyQ (polyglutamine) expansion in the huntingtin protein. Although 
      general brain atrophy is found in HD patients, the striatum is the most severely 
      affected region. Loss or mutant forms of huntingtin were reported to disrupt fast 
      axonal transport in Drosophila, squid, and mice. However, previous work did not 
      resolve whether mutant huntingtin affects global axonal transport or only a 
      subset of cargoes, nor did it resolve whether striatal neurons are preferentially 
      sensitive to huntingtin-mediated defects. We used amyloid precursor protein 
      (APP)-yellow fluorescent protein and brain-derived neurotrophic factor 
      (BDNF)-mCherry fusion proteins as markers for fast axonal transport when 
      huntingtin is altered. We found that movement of APP and BDNF is impaired in 
      striatal and hippocampal, but not cortical, neurons from presymptomatic 
      homozygous mutant mice carrying 150Q huntingtin knock-in mutations. In addition, 
      loss of huntingtin disrupts APP axonal transport, whereas overexpression of 
      wild-type, but not mutant, huntingtin enhances APP transport in all three types 
      of neurons tested. These data suggest that a loss of wild-type huntingtin 
      function in fast axonal transport plays important roles in the development of 
      cell-type-specific defects in HD.
FAU - Her, Lu-Shiun
AU  - Her LS
AD  - Department of Cellular and Molecular Medicine, University of California, San 
      Diego, La Jolla, California 92093, USA.
FAU - Goldstein, Lawrence S B
AU  - Goldstein LS
LA  - eng
GR  - Howard Hughes Medical Institute/United States
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 (Amyloid beta-Protein Precursor)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Htt protein, mouse)
RN  - 0 (Huntingtin Protein)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Nuclear Proteins)
SB  - IM
MH  - Amyloid beta-Protein Precursor/*metabolism
MH  - Animals
MH  - Axonal Transport/*genetics
MH  - Blotting, Western
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Cells, Cultured
MH  - Cerebral Cortex/metabolism
MH  - Corpus Striatum/*metabolism
MH  - Hippocampus/metabolism
MH  - Huntingtin Protein
MH  - Mice
MH  - Mice, Mutant Strains
MH  - Mutation
MH  - Nerve Tissue Proteins/*genetics/metabolism
MH  - Neurons/*metabolism
MH  - Nuclear Proteins/*genetics/metabolism
MH  - Protein Transport/genetics
MH  - Transfection
PMC - PMC6671757
EDAT- 2008/12/17 09:00
MHDA- 2009/01/24 09:00
PMCR- 2009/06/10
CRDT- 2008/12/17 09:00
PHST- 2008/12/17 09:00 [entrez]
PHST- 2008/12/17 09:00 [pubmed]
PHST- 2009/01/24 09:00 [medline]
PHST- 2009/06/10 00:00 [pmc-release]
AID - 28/50/13662 [pii]
AID - 3426520 [pii]
AID - 10.1523/JNEUROSCI.4144-08.2008 [doi]
PST - ppublish
SO  - J Neurosci. 2008 Dec 10;28(50):13662-72. doi: 10.1523/JNEUROSCI.4144-08.2008.