Neuronal pentraxin II is highly upregulated in Parkinson's disease and a novel component of Lewy bodies.

Neuronal pentraxin II (NPTX2) is the most highly upregulated gene in the Parkinsonian substantia nigra based on our whole genome expression profiling results. We show here that it is a novel component of Lewy bodies and Lewy neurites in sporadic Parkinson's disease (PD). NPTX2 is also known as the neuronal activity-regulated protein (Narp), which is secreted and involved in long-term neuronal plasticity.

The medial and lateral substantia nigra in Parkinson's disease: mRNA profiles associated with higher brain tissue vulnerability.

Sporadic Parkinson's disease (PD) is characterized by progressive death of dopaminergic neurons within the substantia nigra. However, pathological cell death within this nucleus is not uniform. In PD, the lateral tier of the substantia nigra (SNl) degenerates earlier and more severely than the more medial nigral component (SNm).

Analysis of alpha-synuclein, dopamine and parkin pathways in neuropathologically confirmed parkinsonian nigra.

The identification of mutations that cause familial Parkinson's disease (PD) provides a framework for studies into pathways that may be perturbed also in the far more common, non-familial form of the disorder. Following this hypothesis, we have examined the gene regulatory network that links alpha-synuclein and parkin pathways with dopamine metabolism in neuropathologically verified cases of sporadic PD. By means of an in silico approach using a database of eukaryotic molecular interactions and a whole genome transcriptome dataset validated by qRT-PCR and histological methods, we found parkin and functionally associated genes to be up-regulated in the lateral substantia nigra (SN).

Glial degeneration and reactive gliosis in alpha-synucleinopathies: the emerging concept of primary gliodegeneration.

The concept of gliodegenerative diseases has not been widely established although there is accumulating evidence that glial cells may represent a primary target of degenerative disease processes. In the central nervous system (CNS), examples that provide a "proof of concept" include at least one alpha-synucleinopathy, multiple system atrophy (MSA), but this disease is conventionally discussed under the heading of "neurodegeneration". Additional evidence in support of primary glial affection has been reported in neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease and transmissible spongiform encephalopathies.

Whole genome expression profiling of the medial and lateral substantia nigra in Parkinson's disease.

We have used brain tissue from clinically well-documented and neuropathologically confirmed cases of sporadic Parkinson's disease to establish the transcriptomic expression profile of the medial and lateral substantia nigra. In addition, the superior frontal cortex was analyzed in a subset of the same cases. DNA oligonucleotide microarrays were employed, which provide whole human genome coverage.