BackgroundHuntington's disease (HD) is a fatal inherited neurodegenerative disease, caused by a

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.

Increased level of MMPs and TIMP-1 of ALS patients may reflect the degeneration process of motor neurons and skeletal muscles and/or is associated with tissues remodeling. The low level of MMP-9 in CSF may result from impaired balance between MMP-9 and TIMP-1 and/or its increased intrathecal degradation and physical clearance. Although the role of changed MMPs/TIMPs level in the pathogenesis of ALS is not clear their analysis in serum may be used as prognostic factor and a potential marker for monitoring treatment effects.

Objective Mutations in the α-synuclein-encoding gene SNCA are considered as a rare cause of Parkinson's disease (PD). Our objective was to examine the frequency of the SNCA point mutations among PD patients of Polish origin. Methods Detection of the known SNCA point mutations A30P (c.88G>C), E46K (c.136G>A) and A53T (c.157A>T) was performed either using the Sequenom MassArray iPLEX platform or by direct sequencing of the SNCA exons 2 and 3. As the two novel substitutions A18T (c.52G>A) and A29S (c.85G>T) were identified, their frequency in a control population of Polish origin was assessed and in silico analysis performed to investigate the potential impact on protein structure and function. Results We did not observe the previously reported point mutations in the SNCA gene in our 629 PD patients; however, two novel potentially pathogenic substitutions A18T and A29S were identified. Each variant was observed in a single patient presenting with a typical late-onset sporadic PD phenotype. Although neither variant was observed in control subjects and in silico protein analysis predicts a damaging effect for A18T and pA29S substitutions, the lack of family history brings into question the true pathogenicity of these rare variants. Conclusions Larger population based studies are needed to determine the pathogenicity of the A18T and A29S substitutions. Our findings highlight the possible role of rare variants contributing to disease risk and may support further screening of the SNCA gene in sporadic PD patients from different populations.

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.

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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.

Lower motor neuron syndromes (LMNS) are heterogenous conditions, which include patients with progressive lower motor neuron disease (LMND) and cases with the clinical phenotype of motor neuropathy (MN). The aim of this study was to estimate the IgM anti-GM1 ganglioside antibodies titer and the ratio of the light chains in order to define the presence of autoimmunity process in particular cases with LMNS. Twenty-eight patients were diagnosed with LMND and 15 patients were diagnosed with MN (10 patients with multifocal motor neuropathy with conduction block, five patients with MN without conduction block). Total of 103 patients with classical amyotrophic lateral sclerosis (ALS) and 50 healthy, age-matched persons were also tested. The IgM anti-GM1 ganglioside titer and the ratio of lambda/kappa light chains in serum were determined using the ELISA technique. High titer of IgM anti-GM1 antibodies were detected in serum of 46% LMND patients, 80% of MN patients, and 18% of the classical ALS cases. An elevated ratio of lambda/kappa light chains appeared in 18% of LMND patients, and in 67% of the MN cases. The lambda/kappa light chains ratio was normal in all ALS patients. The presence of elevated titer of IgM anti-GM1 ganglioside antibodies and the changed ratio of the light chains supports the presence of autoimmune process in LMNS and may provide clues for their management.