Parkinson’s disease (PD) is a major public health problem. Since currently there are no reliable diagnostic tools to reveal the early steps of PD, new methods should be developed, including those searching the variations in human metabolome. Alterations in human metabolites could help to establish an earlier and more accurate diagnosis. The presented research shows a targeted metabolomics study of both of the serum and CSF from PD patients, atypical parkinsonian disorders (APDs) patients, and the control. The use of the LC-MS/MS system enabled to quantitate 144 analytes in the serum and 51 in the CSF. This information about the concentration enabled for selection of the metabolites useful for differentiation between the studied group of patients, which should be further evaluated as candidates for markers of screening and differential diagnosis of PD and APDs. Among them, the four compounds observed to be altered in both the serum and CSF seem to be the most important: tyrosine, putrescine, trans-4-hydroxyproline, and total dimethylarginine. Furthermore, we indicated the metabolic pathways potentially related to neurodegeneration processes. Our studies present evidence that the proline metabolism might be related to neurodegeneration processes underlying PD and APDs. Further studies on the proposed metabolites and founded metabolic pathways may significantly contribute to understanding the molecular background of PD and improving the diagnostics and treatment in the future.

Paraneoplastic movement disorders are rare, autoimmune-mediated, nonmetastatic complications of malignant neoplasms. Common paraneoplastic movement disorders include paraneoplastic chorea, dystonia, cerebellar degeneration, different types of encephalitis, opsoclonus-myoclonus syndrome, stiff person syndrome, and neuromyotonia. Syndromes usually develop before tumor diagnosis, have subacute onset, and are associated with serum or cerebrospinal fluid antibodies. Two types of antibodies can be distinguished: antibodies against nuclear and cytoplasmic neuronal antigens (anti-Hu, anti-Ri, anti-Yo, anti-Ma, anti-CV2/CRMP5, anti-Gephrin, and anti-GABATRAP) and antibodies recently identified against cell surface and synaptic proteins (anti-NMDAR, anti-LGI1, and anti-Caspr2). These two types differ from each other in a few important aspects. Antibodies against cell surface and synaptic protein disrupt cell-surface antigens. Clinical symptoms are related to the disruption of antigens and potentially can be reversed by immunotherapy. The association between these antibodies and malignancy is much less consistent. On the other hand, antibodies against nuclear and cytoplasmic neuronal antigens seem to be not pathogenic; however, they most likely indicate a T-cell-mediated immune response against neurons. Due to T-cell-mediated neuronal loss, response to immunotherapy is generally disappointing. Early recognition of all these diseases is crucial because it may lead to the disclosure of occult cancer. This review is focused on paraneoplastic movement disorders with emphasis on clinical presentations, investigational findings, and therapeutic results.

Neurodegeneration with brain iron accumulation (NBIA) defines a heterogeneous group of progressive neurodegenerative disorders characterized by excessive iron accumulation in the brain, particularly affecting the basal ganglia. In the recent years considerable development in the field of neurodegenerative disorders has been observed. Novel genetic methods such as autozygosity mapping have recently identified several genetic causes of NBIA. Our knowledge about clinical spectrum has broadened and we are now more aware of an overlap between the different NBIA disorders as well as with other diseases. Neuropathologic point of view has also been changed. It has been postulated that pantothenate kinase-associated neurodegeneration (PKAN) is not synucleinopathy. However, exact pathologic mechanism of NBIA remains unknown. The situation implicates a development of new therapies, which still are symptomatic and often unsatisfactory. In the present review, some of the main clinical presentations, investigational findings and therapeutic results of the different NBIA disorders will be presented.

Introduction. Recent instrumentation and software advancement enabled to develop new, high‑throughput targeted metabolomics methods for in‑depth exploration of metabolome in a quantitative manner.Material and Methods. The presented targeted metabolomics approach allows to analyze both of serum and CSF in the same way, with identical sample preparation procedures. The analyses were carried out using high‑performance liquid chromatography system coupled to triple quadrupole tandem mass spectrometer with electrospray ion source (LC‑ESI‑QqQ‑MS/MS). Results. The applied targeted metabolomics approach enabled to determine a wide panel of metabolites from different chemical classes of compounds including: acylcarnitines, amino acids and biogenic amines, glycerophospholipids, sphingolipids and sum of hexoses. Finally, 148 metabolites in serum and 57 in cerebrospinal fluid were determined.Conclusions. Here we presented the results of successful implementation of the method of analysis of low‑molecular weight compounds in human serum and CSF using targeted metabolomics. The evaluation of selected groups of metabolites resulted in obtaining the mean concentrations of panel of metabolites in serum and CSF, which gives a valuable information about the metabolome of these matrices.

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