Parkinson's Disease: Basic Pathomechanisms and a Clinical Overview

PD is a common and a debilitating degenerative movement disorder. The number of patients is increasing worldwide and as yet there is no cure for the disease. The majority of existing treatments target motor symptom control. Over the last two decades the impact of the genetic contribution to PD has been appreciated. Significant discoveries have been made, which have advanced our understanding of the pathophysiological and molecular basis of PD. In this chapter we outline current knowledge of the clinical aspects of PD and the basic mechanistic understanding

Paraoxonase: Its antiatherogenic role in chronic renal failure

Paraoxonase (PON) is an aryldialkylphosphatase, which reversibly binds and hydrolyzes organophosphates. The PON family has three members (PON1, PON2 and PON3); they share structural properties and enzymatic activities. PON1 is shown to reside over high density lipoprotein (HDL) and has both antioxidant and antiatherogenic functions. Function of PON2 and PON3 are speculative and still under research. Several methodologies were developed over the years to determine the activity and mass of PON1, of which spectrophotometer-based methods using certain chemicals as substrate predominate. Several studies have shown decreased levels of PON1 in chronic renal failure (CRF) patients, particularly those on hemodialysis. The role of PON1 in development of cardiovascular disease has drawn considerable attention in recent years. Several authors have shown decreased levels of HDL and PON1 activity in CRF patients on hemodialysis and reported this to be a risk factor in the development of CVD. Enhancement or maintenance of the PON1 activity may prevent development of CVDs and its consequences in patients on hemodialysis

Meta-analysis identifies common and rare variants influencing blood pressure and overlapping with metabolic trait loci.

Meta-analyses of association results for blood pressure using exome-centric single-variant and gene-based tests identified 31 new loci in a discovery stage among 146,562 individuals, with follow-up and meta-analysis in 180,726 additional individuals (total n = 327,288). These blood pressure-associated loci are enriched for known variants for cardiometabolic traits. Associations were also observed for the aggregation of rare and low-frequency missense variants in three genes, NPR1, DBH, and PTPMT1. In addition, blood pressure associations at 39 previously reported loci were confirmed. The identified variants implicate biological pathways related to cardiometabolic traits, vascular function, and development. Several new variants are inferred to have roles in transcription or as hubs in protein-protein interaction networks. Genetic risk scores constructed from the identified variants were strongly associated with coronary disease and myocardial infarction. This large collection of blood pressure-associated loci suggests new therapeutic strategies for hypertension, emphasizing a link with cardiometabolic risk