Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Parkinson's disease is the most frequent movement disorder caused by loss of dopaminergic neurons in the midbrain. Intentions to avoid side effects of the conventional therapy should aim to identify additional targets for potential pharmacological intervention. In principle, every step of a signal transduction cascade such as presynaptic transmitter release, type and occupation of postsynaptic receptors, G protein-mediated effector mechanisms, and the alterations of pre- or postsynaptic potentials as determined by the local ion channel composition, have to be considered. Due to their diversity and their widespread but distinct localizations, potassium channels represent interesting candidates for new therapeutic strategies. As a first step, the present report aimed to study in the striatum the cellular and subcellular distribution of the individual members of the Kir2 family, a group of proteins forming inwardly rectifying potassium channels. For this purpose polyclonal monospecific affinity-purified antibodies against the less conserved carboxyterminal sequences from the Kir2.1, Kir2.2, Kir2.3, and Kir2.4 proteins were prepared. All subunits of the Kir2 family were detected on somata and dendrites of most striatal neurons. However, the distribution of two of them was not homogeneous. Striatal patch areas were largely devoid of the Kir2.3 protein, and the Kir2.4 subunit was most prominently expressed on the tonically active, giant cholinergic interneurons of the striatum. These two structures are among the key players in regulating dopaminergic and cholinergic neurotransmission within the striatum, and therefore are of major importance for the output of the basal ganglia. The heterogeneous localization of the Kir2.3 and the Kir2.4 subunits with respect to these strategic structures pinpoints to these channel proteins as promising targets for future pharmacological efforts.
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PMID:Kir2 potassium channels in rat striatum are strategically localized to control basal ganglia function. 1259 Nov 57

Prior studies have reported gene expression alterations in peripheral blood lymphocytes (PBLs) obtained from patients with Parkinson's disease (PD) as compared to healthy controls. These alterations can not only be regarded as potential biomarkers, but also enhance understanding of the pathogenic mechanism of PD. In the present study, the gene expression levels of dopamine receptor (D2, D3), inward rectified potassium channels subunits Kir2 (Kir2.1, Kir2.2, Kir2.3, Kir2.4) and ATP-sensitive potassium channel subunit Kir6.2 in PBLs were analyzed using quantitative real-time PCR among 20 PD patients with medication, 10 PD patients without medication and 16 healthy controls, respectively. The results showed that there was a significantly decrease of the D2, D3 mRNA expression in PBLs of PD patients compared with that in healthy controls. The four inward rectified potassium channels Kir2.1, Kir2.2, Kir2.3, and Kir2.4 mRNA expression in PBLs from PD patients were also significantly down-regulated than that from age-matched healthy controls. However, there was no apparent difference in expression of another potassium channel Kir6.2 mRNA between PD patients and healthy controls. We proposed that the Kir2 potassium channels mRNA on blood lymphocytes may be regarded as a potential biomarker for PD screening.
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PMID:Verification of expressions of Kir2 as potential peripheral biomarkers in lymphocytes from patients with Parkinson's disease. 2200 75