1,857 research outputs found
Neurocysticercosis Presenting with Epilepsia Partialis Continua: A Clinicopathological Report and Literature Review
No full text
Death-Associated Protein Kinase 1 Variation and Parkinson's Disease
No full textBackground and purpose: Mutations of the LRRK2 gene are now recognized as major risk factors for Parkinson's disease. The Lrrk2 protein is a member of the ROCO family, which also includes Lrrk1 and Dapk1. Functional genetic variants of the DAPK1 gene (rs4877365 and rs4878104) have been previously associated with Alzheimer's disease. Methods: Herein, we assessed the role of DAPK1 variants (rs4877365 and rs4878104) in risk of Parkinson's disease with Sequenom iPLEX genotyping, employing one Taiwanese series (391 patients with Parkinson's disease, 344 controls) and five separate Caucasian series' (combined sample size 1962 Parkinson's disease patients, 1900 controls). Results: We observed no evidence of association for rs4877365 and rs 4878104 and risk of Parkinson's disease in any of the individual series or in the combined Caucasian series under either an additive or recessive model. Conclusion: These specific DAPK1 intronic variants do not increase the risk of Parkinson's disease. However , further functional studies are required to elucidate the potential therapeutic implications with the dimerization of the Dapk1 and Lrrk2 proteins
Catechol-O-Methyltransferase and Parkinson's Disease
No full textParkinson's disease (PD) is one of the main causes of neurological disability in the elderly. Levodopa is the gold standard for treating this disease, but chronic levodopa therapy is complicated by motor fluctuation and dyskinesia. The catechol-O-methyltransferase (COMT) inhibitors represent a new class of antiparkinsonian drugs. When coadministered with levodopa/decarboxylase inhibitor, 2 COMT inhibitors, tolcapone and entacapone have been shown to improve the clinical benefit of levodopa. COMT activity is genetically, polymorphic, and individuals with the low activity (COMTl./l .) genotype have a thermolabile COMT protein; studies suggest that this genotype is less common in Asians than in Caucasians. Differences in COMT activity may determine: the individual response to levodopa and result in ethnic differences in PD susceptibility. Our recent study suggests that the COMTL allele can interact with the MAOB gene to increase the occurrence of PD in Taiwanese. In order to understand this new class of antiparkinsonian drugs, we review their basic properties, pharmacology, and clinical efficacy. The frequency distribution of COMT genetic polymorphisms among different populations and its implications in the etiology and drug response is also discussed
Analysis of Parkin Co-Regulated Gene in a Taiwanese-Ethnic Chinese Cohort with Early-Onset Parkinson's Disease
No full textPArkin Co-Regulated Gene (PACRG) is a novel gene which is transcriptionally co-regulated with the parkin gene (PRKN) by a shared bi- directional promoter. To determine whether mutations in PACRG are associated with early-onset Parkinson 's disease (EO-PD), we performed sequence and dosage analysis of 76 EO-PD patients from a Taiwanese-Ethnic Chinese cohort. This analysis identified two novel nucleotide variants in the non-coding region of PACRG. One patient had an IVS2+247851T>C heterozygous change and two patients had an IVS4+78A>G heterozygous alteration. Neither of these variants was present in the 91 controls tested. A third intronic polymorphism (IVS1+85744insC) was present in cases and controls at an equivalent frequency (approximately 0.25). To facilitate gene dosage analysis, we identified cell lines with a heterozygous deletion or duplication of the entire PACRG locus. Three patients with heterozygous dosage alterations were identified, including two patients with an exon 2 duplication and one patient with an exon 3 deletion of PACRG. No dosage alterations were observed in the 91 controls analyzed (chi(2)=3.66, P=0.056). Our results suggest that point mutations in PACRG are not a common cause of EO-PD but haploinsufficiency for PACRG may be associated with disease
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