Colon may play role in Parkinson's diagnosis

http://edmonton.ctv.ca/servlet/an/local/CTVNews/20120518/parkinsons-colonoscopy-bowel-brain-120527/20120527/?hub=EdmontonHome

But scientists, led by Dr. Kathleen M. Shannon, a neurologist at Rush University Medical Center in Chicago, have stumbled upon what could be an early warning sign of the disease: abnormal chemicals in the colon that can be found two to five years before Parkinson's symptoms even begin.

Dopaminergic neurons for Parkinson's therapy

http://www.nature.com/nbt/journal/v30/n1/full/nbt.2077.html?WT.ec_id=NBT-201201


* Olle Lindvall1

DOI:
doi:10.1038/nbt.2077


A differentiation protocol guided by developmental principles produces more-authentic dopaminergic neurons for transplantation in patients.

A recent report in Nature by Studer and colleagues2 describes the conversion of human embryonic stem cells (hESCs) into substantia nigra dopaminergic neurons that ameliorate Parkinson's disease symptoms in animal models without forming tumors. From the clinical perspective, this new differentiation protocol, which generates large numbers of transplantable dopaminergic neurons of the correct phenotype, represents a major advance toward the first application of hESC-derived dopaminergic neurons for grafting in patients.

A critical issue for clinical translation is safety. The protocol for generating dopaminergic neurons should be fully chemically defined, and the components of animal origin eliminated. The potential for graft-induced dyskinesias after transplantation should be assessed in appropriate animal models.

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

http://www.ncbi.nlm.nih.gov/pubmed/17193926

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 2.0 gene chips. Brain specimens from 21 different brain regions were taken from Parkinson's disease (PD) (n = 22) and normal aged (n = 23) brain donors. The rationale for conducting a multiregional survey of gene expression changes was based on the assumption that if a gene is changed in more than one brain region, it may be a higher probability candidate gene compared to genes that are changed in a single region. Although no gene was significantly changed in all of the 21 brain regions surveyed, we identified 11 candidate genes whose pattern of expression was regulated in at least 18 out of 21 regions. The expression of a gene encoding the mitochondria ribosomal protein S6 (MRPS6) had the highest combined mean fold change and topped the list of regulated genes. The analysis revealed other genes related to apoptosis, cell signaling, and cell cycle that may be of importance to disease pathophysiology. High throughput gene expression is an emerging technology for molecular target discovery in neurological and psychiatric disorders. The top gene reported here is the nuclear encoded MRPS6, a building block of the human mitoribosome of the oxidative phosphorylation system (OXPHOS). Impairments in mitochondrial OXPHOS have been linked to the pathogenesis of PD.

Published studies examining alpha-synuclein expression in Parkinson's Disease

The ups and downs of alpha-synuclein mRNA expression
http://www.ncbi.nlm.nih.gov/pubmed/17094104

- selecting of appropriate "housekeeping" gene for expression normalization is very important
- used four housekeeping genes GAPDH, synaptophysin, HPRT, YWHAZ

brain regions with varying levels of alpha-synuclein pathology:
- occipital lobe (resistant)
- putamen (intermediate)
- amygdala (vulnerable)
- substantia nigra (highly vulnerable)