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1

siRNA skierowane przeciwko telomerazie – skuteczne narzędzie w leczeniu nowotworów?

100%
Rubis B., Polrolniczak A., Rybczynska M.
Postępy Biochemii
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2008
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tom 54
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nr 4
2

Analysis of mutation in SPR and HTRA2 genes in patients with Parkinson’s disease

88%
Polrolniczak A., Dorszewska J., Florczak-Wyspianska J., Owecki M., Kozubski W.
Acta Neurobiologiae Experimentalis
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2013
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tom 73
|
nr 1
Diagnosis of Parkinson’s disease (PD) is often problematic because clinically it can be difficult to distinguish idiopathic PD from the other extrapyramidal disorders. It is known, that PD is caused either by environmental and genetic factors . Genetic mutations are the cause of familial form of PD and include genes PARK1-PARK18. The etiology of sporadic PD (SPD) is still not clear, but it is currently assumed that genetic susceptibilities, may be involved. It is suggested, that in pathogenesis of the SPD beside SNCA and PARK2 genes, may be involved also SPR (sepiapterin reductase gene) [PARK3] and HTRA2 (HTRA serine peptidase 2 gene)[PARK13] genes. The HTRA2 gene, also known as Omi, was found to be associated with PD in German population. However, some studies have indicated that some variants of HTRA2 may not be related to PD. SPR gene, which is located in the PARK3 linkage region is inconsistently associated with a risk of PD but significance of mutations in this gene as well as HTRA2 in PD is still not clear. The aim of the study was the analysis of the frequency of T637A/G SPR as well G421T, G1195A and C1210T mutations in HTRA2 gene in Polish patients with PD and in control group. Peripheral blood was collected from 89 patients with PD clinical diagnosis (42F and 47M, the avr. age 62 ± 10.15 years), and from 113 healthy donors (79F and 7M, the avr. age 55.5 ± 9.54 years). Genomic DNA was isolated using standard protocols. Genotyping was performed by PCR/RFLP using specific primers and restriction enzymes (SsiI, MboII, MvaI, MspI) and sequencing. The SPR gene analysis detected T637A mutation in 3 (3%) PD patients compared to 2 (2%) persons in the control group. Moreover, mutations G421T and G1195A of HTRA2 gene have been identified in 3 (3%) [G421T – 1%, G1195A – 2%] patients with PD and none of controls. Analysis of C1210T HTRA2 mutation detected no mutated variant both in PD patients group and in control group. It was also observed that the stage of the disease was 1–2 in Hoehn and Yahr scale and response to L-dopa was good in patients with T637A SPR and G421T, G1195A HTRA2 mutations. It was also observed some tendency for depression manifestation in PD patients with T637A SPR mutation. It can be concluded, that mutations of SPR and HTRA2 genes probably may be one of the risk factor for manifestation of PD. Thus, the results of this study suggest that analysis of T637A SPR and G421T, G1195A HTRA2 genes mutations may be an additional diagnostic and prognostic factor in PD patients in the future.
3

SNCA, PARK2 and LRRK-2 mutations in Polish patients with sporadic Parkinson’s disease

64%
Polrolniczak A., Dorszewska J., Florczak J., Owecki M., Rozycka A., Rubis B., Jagodzinski P. P., Kozubski W.
Acta Neurobiologiae Experimentalis
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2011
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tom 71
|
nr 1
Parkinson’s disease (PD) is one of the most common neurodegenerative disorders in Poland. Although the genetic basis of familial PD is now well established, the majority of PD is sporadic and occurs without a clear mode of inheritance. The etiology of sporadic PD remains unknown, but it is currently assumed that genetic susceptibilities may be involved. The observation that mutations in α-synuclein (SNCA), parkin (PARK2)and leucine-rich repeat kinase 2 (LRRK2) genes are common in familial PD and increasing evidence supporting a direct role for PARK2 and LRRK-2 in sporadic both early- and late-onset disease make those genes a particularly compelling candidate for intensified investigation. The aim of the study was analysis and identification of SNCA, PARK2 and LRRK-2 mutation in Polish patients with sporadic PD. Peripheral blood was collected from 34 patients with sporadic PD clinical diagnosis (the average age 58 years), and 22 patients with the other neurological diseases (the average age 55 years) as well as from 25 healthy donors (the average age 60 years). Genomic DNA was isolated using standard protocols. SNCA mutations analysis was performed to exclude one of the familial forms of PD. Restriction-enzyme digestion of polymerase-chain reaction (PCR) amplified genomic DNA fragment of SNCA exon 3 detected no G88C mutation. PCR-amplification of parkin exons 2 and 4 also detected no exon deletion. Moreover exon 41 of LRRK-2 gene as well as exons 4, 7 and 11 of PARK2 gene was screened using realtime PCR/HRM and exon sequencing. None of the patients as well as control subjects tested had mutation of LRRK2 gene. These results are consistent with previous reports in the Polish population Mutation in tested exons of PARK2 gene were identified in 20,6% patients with sporadic PD, 4,5% patients with the other neurological disorders and 4,0% control subjects. All detected mutations were heterozygous. One of the PD patients had two mutations in PARK2 gene (G1281A, G601A). It can be concluded, that both G88C SNCA and G2019S LRRK-2 mutations as well as deletion of 2 and 4 exon of parkin gene are rare causes of PD in Poland. Moreover point mutation in PARK2 seems to be associated with sporadic PD in polish population. Thus, the results of this study suggest that screening for PARK2 mutations may be a component of genetic testing for sporadic PD.
4

Memantine up-regulates nicotinic acetylcholine receptors expression in the cortex and sub-cortical white matter of aging rat brain

64%
Polrolniczak A., Rozycka A., Helias-Rodzewicz Z., Kempisty B., Grzelak T., Ziemnicka K., Steinborn B., Jagodzinski P. P., Dorszewska J.
Acta Neurobiologiae Experimentalis
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2013
|
tom 73
|
nr 1
Memantine (MEM) is a potent open channel blocker of N-methyl-Daspartate receptors (NMDARs), and primary has been developed for treatment of neuropathic pain, symptoms of dementia and AD. On the other hand, MEM is able to act as an open channel blocker on several other ligand gated ion channels, e.g., the α4β2 and α7 nicotinic acetylcholine receptors (nAChRs). The aged-related decline in the nAChRs expression could be associated with other senescence markers, such as increased oxidative stress leading to oxidative DNA changes (high level of 8-oxo-2’dG), accompanied with significant decrease in level of the OGG1 protein involved in DNA repair process. To study whether MEM treatment might influence on the α7 and α4 nAChRs expression in the aging rat brain tissues, we analyzed RNA and protein levels by RQ-PCR and Western blot validation in three brain structures: cerebral grey matter (CGM), sub-cortical white matter (SCWM) and cerebellum (Ce) of twenty one female Wistar rats. The animals were divided into following experimental groups: the first group consisted of five 3.0–3.5-month-old females, which was assigned as a young control group, and the remaining sixteen females aged of 18–24 month were divided into three following sub-groups: (1) aged control group of 5 rats; (2) a vehicle group of 5 rats which received intraperitoneal injections of deionized water (3) memantine-treated group of 6 rats. In each group, the selected brain areas have also been analyzed to determinate the levels of oxidative stress. In CGM and SCWM brain structures the level of 8-oxo-2’dG was significantly reduced in old rats after MEM administration (CGM P=0.05; SCWM P<0.05). Western blot analysis has also revealed a significant up-regulation of OGG1 level in CGM after MEM administration (CGM P=0.05). MEM specifically up-regulated mRNA level of cortical α4 subunit in the CGM region of aging rat brain (CGM, P<0.05). In the sub-cortical white matter an important increase of α7 mRNA level has been observed after MEM administration (SCWM P<0.05). The level of α7 nAChR protein was significantly up-regulated also in CGM and Ce regions of MEM treated rats (SCWM P=0.05; CGM P<0.05; Ce P<0.05). We demonstrated that processes related to aging, such as a decreases in OGG1 and nAChRs expression can be modified after memantine administration: (1) A significant increase in the CGM of α4 and α7 subunits, as well as up-regulated α7 level in the SCWM after MEM administration suggests that nAChRs play an important role in compensatory mechanisms facilitating the impaired cholinergic neurotransmission following treatment with MEM. (2) MEM significantly up-regulates cortical OGG1 protein expression and reduces the level of 8-oxo-2’dG in CGM. (3) A significant increase in both mRNA and protein levels of α7 nAChR along with reduction of 8-oxo-2’dG in SCWM, following treatment with MEM, suggests that the effect of MEM on cholinergic function may be associated with antioxidant mechanisms. Whether these protective effects of MEM are direct or are mechanistically remote from NMDARs antagonism, have to be evaluated in the further studies.
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