(1)H magnetic resonance spectroscopy of autosomal ataxias.

Multiple forms of autosomal ataxia exist which can be identified by genetic testing. Due to their wide variety, the identification of the appropriate genetic test is difficult but could be aided by magnetic resonance data. In this study, magnetic resonance spectroscopy (MRS) and imaging (MRI) data were recorded for 20 ataxia patients of six different types and compared to 20 normal subjects. Spectra were acquired in the pons, left frontal lobe, left basal ganglia, left cerebellar hemisphere and vermis. Both metabolite spectra and absolute metabolite concentrations were determined. Differences in metabolite levels were observed between ataxia patients and control subjects and between ataxia patients of different types. A number of correlations were found between metabolite ratios, atrophy levels, number of repeats on the small and large allele, age at examination, symptoms duration and age at symptoms onset for ataxia patients. These MR characteristics are expected to be useful for the identification of the ataxia type.

Characterization of ataxias with magnetic resonance imaging and spectroscopy.

A wide variety of autosomal transmitted ataxias exist and their ultimate characterization requires genetic testing. Common clinical characteristics among different ataxia types complicate the choice of the appropriate genetic test. Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) generally show cerebellar or cerebral atrophy and perturbed metabolite levels which differ between ataxias. In order to help the clinician accurately identify the ataxia type, reported MRI and MRS data in different brain regions are summarized for more than 60 different types of autosomal inherited and sporadic ataxias.

Study of solid-phase synthesis and purification strategies for the preparation of polyglutamine peptides.

Many neurodegenerative diseases are related to an abnormal expansion of the CAG trinucleotide that produces polyglutamine segments in several proteins. However, the pathogenesis of these neurodegenerative states is not yet well understood. Thus, to evaluate the molecular mechanisms leading to those diseases, suitable research tools such as synthetic polyglutamine peptides are required. The synthesis and purification of such peptides are usually difficult because of poor solubility, which leads to low coupling and/or deblocking reactivity. After exploring many synthesis, solubilization and purification approaches, a protocol allowing the production of polyglutamines in good yield and high purity was developed. With this protocol, peptides of 10-30 glutamine residues were synthesized using a linear solid-phase strategy combined with a maximal side-chain protection scheme using fluorenylmethyloxycarbonyl (Fmoc) chemistry. After cleavage of the peptide from the polymeric support, the crude material was treated with glacial acetic acid and lyophilized. This treatment significantly improved the solubility of the polyglutamine peptides thus allowing their dissolution in aqueous conditions and purification through reverse-phase high performance liquid chromatography. These solubilization and purification conditions led to the formation of N-pyroglutamyl peptide derivatives that were easily isolated. These N-pyroglutamylated compounds also appear as useful research tools because data from the literature suggest that N-terminal modification of polyglutamine segments might play a role in their pathogenic properties.