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Partial characterization of the proteome of the mouse striatum
Author(s) -
Guo Ling T.,
Friedmann Theodore,
King Charles C.
Publication year - 2007
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.200700163
Subject(s) - neurodegeneration , striatum , hypoxanthine guanine phosphoribosyltransferase , biology , dopaminergic , dopamine , neuroscience , nigrostriatal pathway , alpha synuclein , basal ganglia , parkinson's disease , medicine , central nervous system , biochemistry , substantia nigra , disease , mutant , gene
Many diseases of the mammalian CNS, including Parkinson's (PD) and Lesch Nyhan disease (LND), are associated with programmatic neurodegeneration or dysfunction of dopaminergic neurons in the mesencephalon, the nigrostriatal pathway, and its projections in the striatum [1–4]. Proteomic studies on brain tissue of both animal models and human PD patients have provided evidence for dysfunction and damage of many pathways, including oxidative stress‐related damage, ubiquitin‐proteasome dysfunction, mitochondrial energy metabolism deficiencies, and synaptic function [5–11]. To date no such proteomic studies have been reported in the related and rare basal ganglia disorder LND, a developmental rather than a neurodegenerative neurological disorder caused by deficiency of the enzyme hypoxanthine‐guanine phosphoribosyltransferase (HPRT) that regulates a major step in the purine salvage pathway [12]. Many studies have demonstrated that the both human LND patients and a mouse knockout model of HPRT deficiency have significantly reduced levels and uptake of dopamine in the striatum [4, 13–16] that is likely to be the principal cause of the CNS disorder. The precise molecular and cellular mechanisms that underlie this neurotransmitter defect are unknown.