Identifying consensus disease pathways in Parkinson's disease using an integrative systems biology approach.

Parkinson's disease (PD) has had six genome-wide association studies (GWAS) conducted as well as several gene expression studies. However, only variants in MAPT and SNCA have been consistently replicated. To improve the utility of these approaches, we applied pathway analyses integrating both GWAS and gene expression.

Gene expression in human hippocampus from cocaine abusers identifies genes which regulate extracellular matrix remodeling.

The chronic effects of cocaine abuse on brain structure and function are blamed for the inability of most addicts to remain abstinent. Part of the difficulty in preventing relapse is the persisting memory of the intense euphoria or cocaine "rush". Most abused drugs and alcohol induce neuroplastic changes in brain pathways subserving emotion and cognition.

A genomic pathway approach to a complex disease: axon guidance and Parkinson disease.

While major inroads have been made in identifying the genetic causes of rare Mendelian disorders, little progress has been made in the discovery of common gene variations that predispose to complex diseases. The single gene variants that have been shown to associate reproducibly with complex diseases typically have small effect sizes or attributable risks. However, the joint actions of common gene variants within pathways may play a major role in predisposing to complex diseases (the paradigm of complex genetics).

Confirmation of region-specific patterns of gene expression in the human brain.

The human brain is divided and categorized in different ways, yet a molecular genetic approach to region specificity does not exist. Using data from 12 healthy control subjects across 18 brain regions, we performed a microarray analysis using both the HG-U133AB and HG-U133 plus 2 chips for each subject to determine molecular targets showing region specificity. Using a previously published data as our guide, we confirm SIX3, GPR6, SH3RF2, and hSyn as molecular markers of the nucleus accumbens and gamma-aminobutyric-acid A receptor alpha-6, Nik-related kinase, and eomesodermin as molecular markers of the cerebellum.

Multiregional gene expression profiling identifies MRPS6 as a possible candidate gene for Parkinson's disease.

Combining large-scale gene expression approaches and bioinformatics may provide insights into the molecular variability of biological processes underlying neurodegeneration. To identify novel candidate genes and mechanisms, we conducted a multiregional gene expression analysis in postmortem brain. Gene arrays were performed utilizing Affymetrix HG U133 Plus 2.

Orexin neurons express a functional pancreatic polypeptide Y4 receptor.

The receptor subtypes that mediate the effects of neuropeptide Y (NPY) on food intake have not been clearly defined. The NPY Y4 receptor has been identified recently as a potential mediator of the regulation of food intake. The purpose of the present study was to characterize the central site of action of the Y4 receptor using a combination of neuroanatomical and physiological approaches.