Linked Life Data

15542714

Source:http://linkedlifedata.com/resource/pubmed/id/15542714

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2004-11-15
pubmed:abstractText
The monoamine neurotoxin methamphetamine (METH) is commonly used as an experimental model for Parkinson's disease (PD). In fact, METH-induced striatal dopamine (DA) loss is accompanied by damage to striatal nerve endings arising from the substantia nigra. On the other hand, PD is characterized by neuronal inclusions within nigral DA neurons. These inclusions contain alpha-synuclein, ubiquitin, and various components of a metabolic pathway named the ubiquitin-proteasome (UP) system, while mutation of genes coding for various components of the UP system is responsible for inherited forms of PD. In this presentation we demonstrate for the first time the occurrence of neuronal inclusions in vivo in the nigrostriatal system of the mouse following administration of METH. We analyzed, in vivo and in vitro, the shape and the fine structure of these neuronal bodies by using transmission electron microscopy. Immunocytochemical investigation showed that these METH-induced cytosolic inclusions stain for ubiquitin, alpha-synuclein, and UP-related molecules, thus sharing similar components with Lewy bodies occurring in PD, with an emphasis on enzymes belonging to the UP system. In line with this, blockade of this multicatalytic pathway by the selective inhibitor epoxomycin produced cell inclusions with similar features. Moreover, using a multifaceted pharmacological approach, we could demonstrate the need for endogenous DA in order to form neuronal inclusions.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0077-8923
pubmed:author
pubmed:issnType
Print
pubmed:volume
1025
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
162-70
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Similarities between methamphetamine toxicity and proteasome inhibition.
pubmed:affiliation
Department of Human Morphology and Applied Biology, University of Pisa, Pisa, Italy. f.fornai@med.unipi.it
pubmed:publicationType
Journal Article