Neurodegeneration – Multimedia

The following case series documents three females admitted to an in-patient unit. All three females had positive HD gene tests and all three had diverse forensic histories. It is recognised that males with HD have an increased forensic risk (Jensen, 1998) but these three cases highlight that HD may also be a forensic risk factor in females.

Random homozygous gene perturbation (RHGP) can identify and validate any host (cellular) gene target that directly causes a desired phenotype without requiring prior knowledge of the target. The central feature of RHGP is a unique lentiviral-based genetic element, known as a gene search vector (GSV) designed to interrogate the entire genome and identify target genes that cause the phenotype of interest.

Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disorder of the CNS. No successful treatment for MS, but one therapeutic strategy in research is the use of bone marrow-derived mesenchymal stem cells (MSC). We studied a group of MS patients who underwented MSCs, assayed for expression of a transcription factor, FOXP3, as a specific marker of MS amelioration in peripheral blood. qRT-PCR on PBMCs showed higher FoxP3 levels.

Spinocerebellar ataxia type 1(SCA1) is an inherited cerebellar neurodegenerative disorder caused by a polyglutamine tract expansion in the ataxin-1 protein.

The University of Kansas in collaboration with PerkinElmer Inc. worked on looking at the comparison of the AlphaLISA Technology and an Electrochemiluminescence Technology to measure assay windows, lower and upper detection limits and intra - and inter-assay precision. In this study, three AlphaLISA no-wash assays, which employ a faster and less complex protocol, were found to deliver highly sensitive and accurate results, equivalent to those obtained in ECL technology.

This study was performed to test the involvement of d-opioid receptors in dyskinesia induced by L-DOPA in hemiparkinsonian rats. Our results indicate that endogenous enkephakins modulate the expression of L-DOPA-induced dyskinesia. It also appears that d-opioid receptors located on corticostriatal terminals could be involved in the development of these dyskinesia. These results confer on d-opioid antagonists interesting properties in the improvement of Parkinson’s disease therapy.

Central nervous system disorders affect many people worldwide. To increase the quality and number of drugs available for treatments of CNS disorders such as Alzheimer’s, schizophrenia and anxiety, the success rate of CNS drug discovery programmes must be improved. The challenge in drug discovery is to develop more relevant assay systems to identify lead compounds for further development. Cell based screening assays currently used for CNS drug development involve primary cells or commercially

Recently, we have presented a strategy to identify new marker molecules characteristic for Alopecia areata by combining protein microarray technology with the use of large cDNA expression libraries (Lueking et al., 2005). This strategy is now applied to Juvenile idiopathic Arthritis (JIA), Rheumatoid Arthritis (RA) and Multiple Sclerosis (MS) in a BMBF-funded project.

Glycogen synthase kinase-3b (GSK-3b ) is a serine/threonine kinase that has recently emerged as a key target for neurodegenerative diseases and diabetes. As an initial step of our lead discovery program we developed a virtual screen to discriminate known GSK-3b inhibitors and inactive compounds using FlexX, FlexX-Pharm and FlexE.