Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2007-1-24
pubmed:abstractText
Mitochondrial dysfunction is implicated in the pathophysiology of Parkinson's disease (PD), a common age-associated neurodegenerative disease characterized by intraneuronal inclusions (Lewy bodies) and progressive degeneration of the nigrostriatal dopamine (DA) system. It has recently been demonstrated that midbrain DA neurons of PD patients and elderly humans contain high levels of somatic mtDNA mutations, which may impair respiratory chain function. However, clinical studies have not established whether the respiratory chain deficiency is a primary abnormality leading to inclusion formation and DA neuron death, or whether generalized metabolic abnormalities within the degenerating DA neurons cause secondary damage to mitochondria. We have used a reverse genetic approach to investigate this question and created conditional knockout mice (termed MitoPark mice), with disruption of the gene for mitochondrial transcription factor A (Tfam) in DA neurons. The knockout mice have reduced mtDNA expression and respiratory chain deficiency in midbrain DA neurons, which, in turn, leads to a parkinsonism phenotype with adult onset of slowly progressive impairment of motor function accompanied by formation of intraneuronal inclusions and dopamine nerve cell death. Confocal and electron microscopy show that the inclusions contain both mitochondrial protein and membrane components. These experiments demonstrate that respiratory chain dysfunction in DA neurons may be of pathophysiological importance in PD.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/17227870-10506125, http://linkedlifedata.com/resource/pubmed/commentcorrection/17227870-11062475, http://linkedlifedata.com/resource/pubmed/commentcorrection/17227870-11182476, http://linkedlifedata.com/resource/pubmed/commentcorrection/17227870-11259653, http://linkedlifedata.com/resource/pubmed/commentcorrection/17227870-11588181, http://linkedlifedata.com/resource/pubmed/commentcorrection/17227870-11744721, http://linkedlifedata.com/resource/pubmed/commentcorrection/17227870-12059041, http://linkedlifedata.com/resource/pubmed/commentcorrection/17227870-12068295, http://linkedlifedata.com/resource/pubmed/commentcorrection/17227870-12388586, http://linkedlifedata.com/resource/pubmed/commentcorrection/17227870-12417746, http://linkedlifedata.com/resource/pubmed/commentcorrection/17227870-12971891, http://linkedlifedata.com/resource/pubmed/commentcorrection/17227870-14597761, http://linkedlifedata.com/resource/pubmed/commentcorrection/17227870-14978272, http://linkedlifedata.com/resource/pubmed/commentcorrection/17227870-15016765, http://linkedlifedata.com/resource/pubmed/commentcorrection/17227870-15164064, http://linkedlifedata.com/resource/pubmed/commentcorrection/17227870-15294138, http://linkedlifedata.com/resource/pubmed/commentcorrection/17227870-15576046, http://linkedlifedata.com/resource/pubmed/commentcorrection/17227870-15790530, http://linkedlifedata.com/resource/pubmed/commentcorrection/17227870-16260631, http://linkedlifedata.com/resource/pubmed/commentcorrection/17227870-16332961, http://linkedlifedata.com/resource/pubmed/commentcorrection/17227870-16449387, http://linkedlifedata.com/resource/pubmed/commentcorrection/17227870-16604074, http://linkedlifedata.com/resource/pubmed/commentcorrection/17227870-16647881, http://linkedlifedata.com/resource/pubmed/commentcorrection/17227870-16672980, http://linkedlifedata.com/resource/pubmed/commentcorrection/17227870-16672981, http://linkedlifedata.com/resource/pubmed/commentcorrection/17227870-7566680, http://linkedlifedata.com/resource/pubmed/commentcorrection/17227870-7637582, http://linkedlifedata.com/resource/pubmed/commentcorrection/17227870-8650242, http://linkedlifedata.com/resource/pubmed/commentcorrection/17227870-9500544, http://linkedlifedata.com/resource/pubmed/commentcorrection/17227870-9501743, http://linkedlifedata.com/resource/pubmed/commentcorrection/17227870-9916792, http://linkedlifedata.com/resource/pubmed/commentcorrection/17227870-9916807
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0027-8424
pubmed:author
pubmed:issnType
Print
pubmed:day
23
pubmed:volume
104
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1325-30
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Progressive parkinsonism in mice with respiratory-chain-deficient dopamine neurons.
pubmed:affiliation
Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital, S-14186 Stockholm, Sweden.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural