Amino acids play numerous roles in the central nervous system, serving as neurotransmitters, neuromodulators and regulators of energy metabolism. The free amino acid profile in serum of Parkinson’s disease (PD) patients may be influenced by neurodegeneration, mitochondrial dysfunction, malabsorption in the gastroenteric tract and received treatment. The aim of our study was the evaluation of the profile of amino acid concentrations against disease progression. We assessed the amino acid profile in the serum of 73 patients divided into groups with early PD, late PD with dyskinesia and late PD without dyskinesia. Serum amino acid analysis was performed by high-pressure liquid chromatography with fluorescence detection. We observed some significant differences amongst the groups with respect to concentrations of alanine, arginine, phenylalanine and threonine, although no significant differences were observed between patients with advanced PD with and without dyskinesia. We conclude that this specific amino acid profile could serve as biochemical marker of PD progression.

In amyotrophic lateral sclerosis (ALS), a neurodegenerative disease of unknown origin, excitotoxic mechanisms are supposed to be involved. Divergent results are, however, presented either because of the heterogeneity of this disease, and/or different methodologies used to evaluate the excitotoxic amino acids content. The results of the most sensitive high performance liquid chromatography (HPLC) techniques with precolumn derivatization of fasting serum and CSF glutamate, aspartate, glycine and gamma-aminobutyric acid (GABA) in mild and severely progressing ALS cases are presented here. We studied 25 ALS patients with different course of the disease and controls, which consisted of 10 cases with other motor neuron diseases and 20 healthy, age-matched subjects. In the ALS patients with a mild course of the disease serum glutamate and aspartate content was either normal or slightly decreased, in all of these cases a rise in GABA and glycine was present. In the severely progressing ALS cases serum glutamate and aspartate was increased. The GABA content was either normal or increased, the glycine level appeared to be either normal or decreased. In CSF the amino acids changes in ALS were less pronounced as compared to serum. The most frequent finding was the increase in GABA concentration both in the mild and the severely progressing group. CSF glutamate in ALS patients with mild course of the disease was decreased, in the severely progressing cases the glutamate level appeared in a broad range from decreased to increased values. CSF aspartate was either normal or elevated, glycine values were present in a broad range from decreased to increased values. In the other tested motor neuron diseases no consistent changes in serum and CSF amino acids concentration was observed. The data from serum and CSF indicate that in ALS an imbalance between excitatory and inhibitory amino acids might be present in the brain, which may be induced in different ways in particular ALS patients. It may be an important factor for the mediation of neurons death.

Objectives - An autoimmune basis has been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). This hypothesis is supported by the presence of antibodies that interact with motoneuron antigens in serum of these patients. Against autoimmunity are the discrepances in the frequency of the antibodies appearance and also failure of immunosuppression. The aim of our study was to evaluate the titer of antibodies against GM1-gangliosides, AGM1-gangliosides and anti-sulfatides in paired serum and cerebrospinal fluid samples in the ALS patients. Material and methods - Serum of 103 and CSF of 79 patients with ALS was examined. The “disease controls” consisted of 22 cases of other motor neuron diseases and 50 healthy, age-matched normals. CSF was drawn at the same time from 79 ALS patients, 6 cases of the “disease controls” and 50 normals. To study the titer of antibodies against GM1-gangliosides, AGM1-gangliosides and sulfatides the ELISA technique has been applied. Results - An increased titer against GM1-gangliosides, AGM1-gangliosides and sulfatides in ALS appeared in serum in 18%, 32% and 11%, resp., in the “disease controls” the increased antibodies titer appeared in single cases. In CSF the appropriate values in ALS were 20%, 15%, 8%, resp. In the “disease controls” a high antibodies titer was a rare finding. Conclusions - It is concluded that in some ALS cases and also in some patients with other motor neuron diseases an autoimmune mechanism may contribute to motor neuron injury.

Parkinson’s disease (PD) is generally considered a sporadic disorder, but a strong genetic background is often found. The aim of this study was to identify the underlying genetic cause of PD in two affected siblings and to subsequently assess the role of mutations in Cathepsin B (CTSB) in susceptibility to PD. A typical PD family was identified and whole-exome sequencing was performed in two affected siblings. Variants of interest were validated using Sanger sequencing. CTSB p.Gly284Val was genotyped in 2077 PD patients and 615 unrelated healthy controls from the Czech Republic, Ireland, Poland, Ukraine, and the USA. The gene burden analysis was conducted for the CTSB gene in an additional 769 PD probands from Mayo Clinic Florida familial PD cohort. CTSB expression and activity in patient-derived fibroblasts and controls were evaluated by qRT-PCR, western blot, immunocytochemistry, and enzymatic assay. The CTSB p.Gly284Val candidate variant was only identified in affected family members. Functional analysis of CTSB patient-derived fibroblasts under basal conditions did not reveal overt changes in endogenous expression, subcellular localization, or enzymatic activity in the heterozygous carrier of the CTSB variant. The identification of the CTSB p.Gly284Val may support the hypothesis that the CTSB locus harbors variants with differing penetrance that can determine the disease risk.