Preferred Label : Parkinson's Disease Pathway BioCarta;
NCIt synonyms : BioCarta Parkinsons Disease Pathway;
NCIt related terms : Alpha-synuclein and Parkin-mediated proteolysis in Parkinson's disease;
Alternative definition : BIOCARTA: The motor defects of Parkinson's disease are related to the loss of dopaminergic
neurons in specific brain regions. Examination of these neurons in diseased tissue
has revealed the presence of Lewy bodies, dense aggregates that include the protein
alpha-synuclein. A genetic basis for most cases of Parkinson's disease has not yet
been identified, but mutations in alpha-synuclein have been associated with at least
one rare form of the disease, and mutations in another protein, the parkin gene, are
associated with another inherited form of Parkinson's disease. Parkin is found in
Lewy bodies along with alpha-synuclein and the parkin protein is an enzyme, an E3
ubiquitin ligase. This ligase tags specific proteins in normal cells with ubiquitin,
targeting them for destruction in the proteasome. One of the proteins that parkin
normally targets for destruction is a specific O-glycosylated form of alpha-synuclein.
Failure of parkin-mediated degradation of alpha-synuclein may be a key factor leading
to the death of dopaminergic neurons. Another substrate of parkin is a GPCR-like protein
called Pael-R that accumulates in the ER of affected cells and may cause neuronal
cell death. The involvement of Parkin and alpha-synuclein mutations in genetic forms
of Parkinson's suggests that failure of ubiquitination and protein degradation may
be causative in other forms of Parkinson's. Questions remaining include the cause
of the lack of effective ubiquitination in individuals lacking obvious genetic defects
in this pathway and how to use this knowledge of ubiquitination and protein degradation
in Parkinson's disease to identify therapeutic strategies. (This definition may be
outdated - see the DesignNote.);
NCIt note : The BIOCARTA Definition (ALT_DEFINITION) for this pathway concept was provided by
BioCarta. This property was not created by, nor is it maintained by the NCI Thesaurus
staff. Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA
Definition might be outdated or inaccurate. Please see the Terms and Conditions for
Use at http://www.biocarta.com/.;
Biocarta ID : h_ParkinsonsPathway;
Origin ID : C39276;
UMLS CUI : C1511121;
Semantic type(s)
- has_gene_product_element
- pathway_has_gene_element
