Papers by Sergei Illarioshkin
Neurology, 2017
Objective: To do a pilot retrospective research of Huntington disease (HD) prevalence in Russia. ... more Objective: To do a pilot retrospective research of Huntington disease (HD) prevalence in Russia. Background: Prevalence of HD varies across countries/regions. Four systematic reviews on worldwide prevalence (per 100,000 of the population) were published showing the least values in Asia (0.4) and the highest — in North America (7.33) and the UK (6.68). Only one by Rawlins et al. included Russia in analysis. However, because the majority of Russian epidemiological studies were published in Russian, only five small studies on HD prevalence were used by the authors Design/Methods: We searched in PubMed, eLIBRARY.RU platform, and in Russian State Library catalog for all works with estimation of HD prevalence in Russian regions which were published both in English and Russian after 1994 when genetic testing for HD became available in Russia. We implemented meta-analysis procedure using Freeman-Tukey transformation under random effect model with REML method. Results: 22 epidemiological stu...
Neurology, 2017
Objective: (1) To assess whether data collected during Enroll-HD visits are sufficient to study e... more Objective: (1) To assess whether data collected during Enroll-HD visits are sufficient to study effects of tetrabenazine and olanzapine in Huntington disease (HD) and (2) to evaluate influence of these medicines on UHDRS motor scores and PBAs depression score. Background: To date, only tetrabenazine is approved for treatment of chorea in HD. However, despite of lack of evidence, a variety of other medicines, including neuroleptics, are used off-label for the same indication. Olanzapine is one of the often prescribed neuroleptics in HD. To our knowledge, no comparisons of any kind of tetrabenazine and olanzapine have been done so far — only one comparative clinical trial NEUROHD (NCT00632645) is still ongoing without any published data. Design/Methods: Of 2295 HD manifest subjects from the Enroll-HD R2 database only 17 patients on tetrabenazine and 24 on olanzapine fulfilled the criteria to be off antichoreatic medication (AM) at the first assessment (FA) and on AM at the second asse...
Aging Health, 2009
Transcranial sonography has become a useful tool in the differential diagnosis of parkinsonian sy... more Transcranial sonography has become a useful tool in the differential diagnosis of parkinsonian syndromes. This is a non-invasive, low cost procedure. The main finding on transcranial sonography in patients with idiopathic Parkinson's disease is an increased echogenicity of the mesencephalic substantia nigra region. This hyperechogenicity is present in more than 90% of cases, and reflects a dysfunction in the dopaminergic nigrostriatal pathway. This study discussed how the hyperechogenicity of the substantia nigra may facilitate the differential diagnosis of parkinsonian syndromes.
Background: One of the causes of Parkinson's disease is mutations in the PARK2 gene. Deletions an... more Background: One of the causes of Parkinson's disease is mutations in the PARK2 gene. Deletions and duplications of single exons or exon groups account for a large proportion of the gene mutations. Direct detection of these mutations can be used for the diagnosis of Parkinson's disease. Methods: To detect these mutations, we developed an effective technique based on the real-time TaqMan PCR system, which allows us to evaluate the copynumbers of the PARK2 gene exons by comparing the intensity of the amplification signals from some exon of this gene with that of the βglobin gene (the internal control). Results: We analyzed rearrangements in exons 1-12 of the PARK2 gene in 64 patients from Russia with early-onset Parkinson's disease. The frequency of these mutations in our patients was 14%. Conclusion: We have developed a simple, accurate, and reproducible method applicable to the rapid detection of exon rearrangements in the PARK2 gene. It is suitable for the analysis of large patient groups, and it may become the basis for a diagnostic test.
Journal of Neurology Research
Parkinson's disease (PD) is a systemic neurodegenerative disease characterized by tremor, rigidit... more Parkinson's disease (PD) is a systemic neurodegenerative disease characterized by tremor, rigidity, bradykinesia, and stooping posture. When more than 60% of dopaminergic neurons in the substantia nigra of the brain have died, motor symptoms manifest in PD. Currently, oxidative stress (OS) is considered to be one of the leading factors provoking death of dopaminergic neurons in PD. This review is concerned with the role of polyamines in PD, especially focusing on their role in OS induction. Polyamines (putrescine, cadaverine, spermidine and spermine) are involved in many molecular mechanisms, including cell proliferation and differentiation, gene transcription and translation, modulation of the functional activity of ion channels and receptors, and other vital processes. It is worth noting that under physiological conditions polyamines are antioxidants. It has been shown that spermine oxidase (SMOX) is up-regulated in PD, activating polyamine breakdown, which leads to excessive formation of toxic aldehydes (such as acrolein), H 2 O 2 (a strong cytostatic) and ammonia (a toxic substance). Polyamines are also involved in the pathogenetic mechanism of α-synuclein modification resulting in the formation of Lewy bodies. This review provides data on the changes in polyamine levels at later stages of the disease. The review also examines the role of polyamines, as gliotransmitters, in regulating neural function and vice versa. The mechanisms of polyamine "pumping" from neurons to glia can be considered factors of OS regulation in neurons. Prolonged accumulation of polyamines in glia can lead to oxidation of polyamines and therefore potentially to gliosis in PD. The exact mechanisms of this process are, however, not clear. Answering the questions regarding the role of polyamines in gliosis development and pathogenesis of PD is necessary for treating cognitive impairment in patients with PD, which is particularly important.
Frontiers in aging neuroscience, 2018
Background: Parkinson's disease (PD) is a complex disease with its monogenic forms accounting for... more Background: Parkinson's disease (PD) is a complex disease with its monogenic forms accounting for less than 10% of all cases. Whole-exome sequencing (WES) technology has been used successfully to find mutations in large families. However, because of the late onset of the disease, only small families and unrelated patients are usually available. WES conducted in such cases yields in a large number of candidate variants. There are currently a number of imperfect software tools that allow the pathogenicity of variants to be evaluated. Objectives: We analyzed 48 unrelated patients with an alleged autosomal dominant familial form of PD using WES and developed a strategy for selecting potential pathogenetically significant variants using almost all available bioinformatics resources for the analysis of exonic areas. Methods: DNA sequencing of 48 patients with excluded frequent mutations was performed using an Illumina HiSeq 2500 platform. The possible pathogenetic significance of identified variants and their involvement in the pathogenesis of PD was assessed using SNP and Variation Suite (SVS), Combined Annotation Dependent Depletion (CADD) and Rare Exome Variant Ensemble Learner (REVEL) software. Functional evaluation was performed using the Pathway Studio database. Results: A significant reduction in the search range from 7082 to 25 variants in 23 genes associated with PD or neuronal function was achieved. Eight (FXN, MFN2, MYOC, NPC1, PSEN1, RET, SCN3A and SPG7) were the most significant. Conclusions: The multistep approach developed made it possible to conduct an effective search for potential pathogenetically significant variants, presumably involved in the pathogenesis of PD. The data obtained need to be further verified experimentally.
Voprosy medit͡sinskoĭ khimii
ABSTRACT
Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova / Ministerstvo zdravookhraneniia i meditsinskoi promyshlennosti Rossiiskoi Federatsii, Vserossiiskoe obshchestvo nevrologov [i] Vserossiiskoe obshchestvo psikhiatrov
Hepatolenticular degeneration (HLD) is a severe autosomal-recessive disorder of the copper metabo... more Hepatolenticular degeneration (HLD) is a severe autosomal-recessive disorder of the copper metabolism. It is characterized by excessive accumulation of copper in the brain and in viscera and is conditioned by the damage in the gene of copper ATP-ase (ATP7B). The paper presents the results of screening of ATP7B gene mutation in 42 patients with HLD from Russian population. The regions of ATP7B gene that are the most frequently exposed to the mutation have been studied (the exzones 14, 15, 16, 18). It is demonstrated that A-->C mutation in the 14-th exzone that led to the change of histidine1069 amino acid for glutamine, was found in more than 60% of patients--Slavs from the European Russia. This mutation was observed in both homo- and heterozygous states. The deletion of (CCC-->CC) nucleotide in the 15-th exzone of the gene was observed in 2 cases. The detailed analysis of the clinical-genetic correlations was performed in patients with the determined damages of ATP7B gene. In Russia the experience of the direct DNA-diagnosis of HLD is described for the first time. It is significant for early evaluation of the patients in preclinical state and for prescription of the preventive copper-eliminating therapy.
Background / Purpose: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease ch... more Background / Purpose: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive loss of upper and lower motor neurons, the development of paralyses, and death from respiratory and bulbar failure. 10% of ALS cases are familial. Mutations in 18 gene loci could determine the ALS and more than 25 proteins are involved in ALS pathogenesis. Main conclusion: The spectrum of SOD1 and ANG mutations was analysed for the first time in Russian population of ALS patients. High frequency of SOD1 mutations in familial ALS was detected. The absence of cording TARDBP mutation was observed. Some significant associations were detected. The results of in silico analysis of the SOD1 gene mutations confirm the position of ALS within the class of conformational diseases.
Genetika
The Huntington's chorea mutation consists of expansion of trinucleotide CAG repeats in the re... more The Huntington's chorea mutation consists of expansion of trinucleotide CAG repeats in the recently discovered gene IT-15. In this work, for the first time in a population of Russian patients, correlations between the number of copies of CAG repeats and various clinical characteristics of the disease are investigated. It is established that the degree of triplet expansion determines the age of onset of the disease and the rate of progression of the neurological and mental symptoms of Huntington's chorea, and it is also shown that the genetic instability of the mutant allele is considerably higher upon transmission of the disease gene along the paternal line. We obtained direct confirmation of the possibility of genetic instability of a normal allele inherited paternally. In this work, the first successful direct (including preclinical) DNA diagnosis in Russia of Huntington's chorea was obtained.
Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova / Ministerstvo zdravookhraneniia i meditsinskoi promyshlennosti Rossiiskoi Federatsii, Vserossiiskoe obshchestvo nevrologov [i] Vserossiiskoe obshchestvo psikhiatrov
The results of treatment with noben (idebenon), an improved structural analogue of coenzyme Q10, ... more The results of treatment with noben (idebenon), an improved structural analogue of coenzyme Q10, of 34 patients with Friedrich's disease are presented. In all cases, the clinical diagnosis was confirmed by the presence of a typical mutation, an expansion of trinucleotide GAA-repeats, in the FRDA gene. All patients received noben as a main drug in dosage 5 mg/kg daily during 3 months. An examination of the patients included modern laboratory and instrumental methods, analysis of levels of lactic and pyruvic acids and their ratio in the peripheral blood. Also parameters of lipid peroxidation and mitochondrial dehydrogenase activity in peripheral lymphocytes were studied. Positive changes were found in the majority of patients for muscle strength in extremities, tolerability to physical loadings, general fatigue, movement activity, speech and coordination functions, along with significant improvement of biochemical and cytochemical status. The results obtained suggest a positive ef...
Neurochemical Journal, 2012
Our review is focused on new aspects of the pathogenesis of amyotrophic lateral sclerosis (ALS); ... more Our review is focused on new aspects of the pathogenesis of amyotrophic lateral sclerosis (ALS); it considers the hypothesis that disturbances in transcription have a substantial role in ALS. We described the func tions of ALS related genes whose protein products are involved in various processes of mRNA metabolism. We present modern concepts on the functions of the DNA/RNA binding proteins TDP43 and FUS which, according to many researchers, are key participants in the development of the neurodegenerative process.
Molekuliarnaia biologiia
Parkinson's disease (PD) is the second most common progressive neurodegenerative disorder cha... more Parkinson's disease (PD) is the second most common progressive neurodegenerative disorder characterized by the degeneration of dopaminergic neurons. Detecting changes in gene expression in untreated de novo patients with PD is important for understanding disease pathogenesis and for identifying biomarkers for preclinical stage of PD. In this study we investigate expression of gene of Glycogen synthase kinase-3 beta (GSK3B) in the peripheral blood of different groups of patients with neurological diseases using reverse transcription reaction and real-time polymerase chain reaction (PCR). Our results suggest that the expression levels of GSK3B can't serve as a biomarker for early stages of PD.
Journal of neurology, 2000
Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova / Ministerstvo zdravookhraneniia i meditsinskoĭ promyshlennosti Rossiĭskoĭ Federatsii, Vserossiĭskoe obshchestvo nevrologov [i] Vserossiĭskoe obshchestvo psikhiatrov, 1996
At least 5 different genes of autosomal dominant spinocerebellar ataxias (SCA) were revealed rece... more At least 5 different genes of autosomal dominant spinocerebellar ataxias (SCA) were revealed recently. Their discovery permitted to elaborate the most perfect classification of this heterogeneous group of diseases. In two forms of ataxias (SCA1 and SCA3) the mutations consist in the expansion of CAG-trinucleotides repetitions. The Russian population of patients with dominant SCA (13 families) was examined for the first time in terms of the evaluation of mutant gene carriers of SCA1 and SCA3. SCA1 was diagnosed in 5 families on the molecular level. The cerebellar ataxia, dysarthria as well as pyramidal symptoms comprised the basis of SCA1 clinical pattern. There were no SCA3 cases at DNA-testing. The perspectives of DNA-diagnosis of inherited ataxias were considered.
Molekuliarnaia genetika, mikrobiologiia i virusologiia, 2014
The Parkinson disease (PD) is a severe neurological disorder. Diverse genetic systems and environ... more The Parkinson disease (PD) is a severe neurological disorder. Diverse genetic systems and environmental factors are involved in the pathogenesis of this disease. However, despite extensive research into the disease, its causes are not fully elucidated, and the exact spectrum of genes and mutations involved in the development of hereditary forms of PD has not been fully clarified yet. The present work is devoted to the analysis of mutations that lead to the development of monogenic forms of PD in patients with suspected autosomal dominant form of PD using Multiplex Ligation-dependent Probe Amplification (MLPA). We have identified several mutations (G2019S in LRRK2, heterozygous deletions of 2-3, 3-4 exons and heterozygous duplication of 2-4 exons in PARK2, deletion of 3 exon in PARK7) that lead to the development of PD in only 7 people out of 70 (18.4%), which suggests the need for further search of new mutations, for example, using exome sequencing. In the future it will help to dev...
![Research paper thumbnail of [Association between the VEGF -2578С/A polymorphism and amyotrophic lateral sclerosis in a Russian population]](https://attachments.academia-assets.com/67946058/thumbnails/1.jpg)
Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova / Ministerstvo zdravookhraneniia i meditsinskoĭ promyshlennosti Rossiĭskoĭ Federatsii, Vserossiĭskoe obshchestvo nevrologov [i] Vserossiĭskoe obshchestvo psikhiatrov, 2012
Genetic predisposition plays an important role in the development of amyotrophic lateral sclerosi... more Genetic predisposition plays an important role in the development of amyotrophic lateral sclerosis (ALS). One of the most promising candidate genes in ALS is the vascular endothelial growth factor (VEGF) gene. In a Russian population, 192 ALS patients (103 males and 89 females), aged from 20 to 83 years (52.0±13.4), were examined. A control group comprised 128 age- and sex-matched people. All individuals studied were Slavs. Polymorphism -2578С/А (rs699947) in the VEGF gene was studied by real-time PCR. It was shown that the genotype distribution was significantly different between the ALS and control groups (χ2=11.1; р=0.004); in the ALS cohort, the 2578A/A genotype was significantly more frequent (29.7% vs. 20.3%, p=0.04). The allele distribution was also significantly different between the two groups (χ2=4.4; р=0.036). The -2578А/А genotype increased risk of ALS (OR 1.66; 95% CI 1.03-2.29), and this pattern was most obvious in the male subgroup (OR=2.18; 95% CI 1.90-2.47). It was ...
Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova / Ministerstvo zdravookhraneniia i meditsinskoĭ promyshlennosti Rossiĭskoĭ Federatsii, Vserossiĭskoe obshchestvo nevrologov [i] Vserossiĭskoe obshchestvo psikhiatrov, 2010
Hereditary spastic paraplegia (HSP), type 4, or SPG4, caused by various mutations in the spastin ... more Hereditary spastic paraplegia (HSP), type 4, or SPG4, caused by various mutations in the spastin gene (SPAST) is the most common disorder in a heterogeneous group of autosomal dominant HSP's. We performed a search of SPAST mutations by routine methods (SSCP and subsequent direct sequencing of fragments with modified electrophoretic mobility) in a sample of 26 families with autosomal dominant HSP from different Russian regions. In six families, five of Russian and one of Tatar ethnicity, different SPAST mutations were detected. Three of the mutations, Arg431Stop, Gln280Arg FsX9 and Asn386Ser, were reported previously; the remaining three, Asp555Tyr, Thr369Thr and Asn184Thr, were novel. In the family with the Arg431Stop mutation, a linkage to SPG4 locus was also established, lod scores were 1,66 for D2S352 marker and 1,51 for D2S367. Another large family also showed a linkage to the SPG4 locus (lod scores 1,68 for D2S352, 2,17 for D2S367) but the mutation was not found which may b...
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Papers by Sergei Illarioshkin