Reply to: “Increased alpha‐Synuclein Level in CD45 + Blood Cells in Asymptomatic Carriers of GBA Mutations”

2021 ◽  
Vol 36 (8) ◽  
pp. 1998-1999
Author(s):  
Micol Avenali ◽  
Silvia Cerri ◽  
Fabio Blandini
Keyword(s):  
Blood Cells ◽  
Alpha Synuclein ◽  
Asymptomatic Carriers ◽  
Gba Mutations

Expression of alpha-synuclein gene and genes of lysosomal membrane proteins and enzymes in Parkinson’s disease associated with mutation in the GBA gene

2020 ◽  
pp. 107-108
Author(s):  
Т.С. Усенко ◽  
А.И. Безрукова ◽  
Д.А. Богданова ◽  
К.А. Сенкевич ◽  
А.В. Кудреватых ◽  
...  
Keyword(s):  
Risk Factor ◽  
Membrane Proteins ◽  
Genetic Risk ◽  
Blood Cells ◽  
Lysosomal Enzymes ◽  
Alpha Synuclein ◽  
Mrna Levels ◽  
Gba Gene ◽  
Lysosomal Membrane Proteins ◽  
Gba Mutations

Мутации в гене, кодирующем лизосомный фермент глюкоцереброзидазу (GBA), являются фактором высокого риска болезни Паркинсона (БП). Остается неясным, почему не у всех носителей мутаций в данном гене в течение жизни развивается БП. Предполагается, что дисфункция мембранных белков и ферментов лизосом может способствовать развитию БП у носителей мутаций в гене GBA. В данном исследовании была оценена экспрессия генов альфа-синуклеина и LAMP2, GLA, GALNS, SCARB2 в CD45+ клетках периферической крови у пациентов с GBA-БП, бессимптомных носителей мутаций в гене GBA (GBA-носителей), а также в у пациентов с БП и в контроле. Выявлена повышенная экспрессия гена альфа-синуклеина на фоне снижения уровня экспрессии генов мембранных белков лизосом (LAMP2, SCARB2) у пациентов с GBA-БП и GBA-носителей, что может свидетельствовать о вовлеченности этих генов в патогенез GBA-БП. Пониженная экспрессия гена LAMP2 может рассматриваться в качестве одного из триггеров развития БП у носителей мутаций в гене GBA. Mutations in the gene GBA that are encoding the lysosomal enzyme glucocerebrosidase are the most common genetic risk factor for PD. Not every carrier of GBA mutations will develop PD. Probably the dysfunction of lysosomal enzymes and membrane proteins may contribute or protect to the development of PD among carriers of GBA mutations. In the current study LAMP2, GLA, GALNS, SCARB2 and alpha-synuclein mRNA levels in CD45+ blood cells were estimated in patients with GBA-associated PD (GBA-PD), non-manifesting GBA carriers(GBA-Carriers), PD patients and controls. This is the first report estimating LAMP2, GLA, GALNS, SCARB2 and alpha-synuclein expressions in CD45+ blood cells in GBA-PD patients and GBA-Carriers. We revealed increased SNCA expression and changing expression of lysosomal genes (LAMP2, GALNS, SCARB2) that may contribute role these genes in pathogenesis of GBA-PD. Decreased of LAMP2 may be considered as trigger of GBA-PD.

Increased α‐Synuclein Level in CD45 + Blood Cells in Asymptomatic Carriers of GBA Mutations

2021 ◽  
Vol 36 (8) ◽  
pp. 1997-1998
Author(s):  
Anton Emelyanov ◽  
Tatiana Usenko ◽  
Mikhail Nikolaev ◽  
Konstantin Senkevich ◽  
Darya Kulabukhova ◽  
...  
Keyword(s):  
Blood Cells ◽  
Asymptomatic Carriers ◽  
Gba Mutations

P.0747 The CD45+ blood cells alpha-synuclein concentration in synucleinopathies

2021 ◽  
Vol 53 ◽  
pp. S543-S544
Author(s):  
A. Zhuravlev ◽  
A. Lavrinova ◽  
D. Kulabuhova ◽  
M. Nikolaev ◽  
H. Fayud ◽  
...  
Keyword(s):  
Blood Cells ◽  
Alpha Synuclein

scholarly journals GBA Mutations Influence the Release and Pathological Effects of Small Extracellular Vesicles from Fibroblasts of Patients with Parkinson’s Disease

2021 ◽  
Vol 22 (4) ◽  
pp. 2215
Author(s):  
Silvia Cerri ◽  
Cristina Ghezzi ◽  
Gerardo Ongari ◽  
Stefania Croce ◽  
Micol Avenali ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Extracellular Vesicles ◽  
Molecular Mechanisms ◽  
Fibroblast Cell ◽  
Alpha Synuclein ◽  
Gene Encoding ◽  
Gba Gene ◽  
The Impact ◽  
Gba Mutations

Heterozygous mutations in the GBA gene, encoding the lysosomal enzyme glucocerebrosidase (GCase), are the strongest known genetic risk factor for Parkinson’s disease (PD). The molecular mechanisms underlying the increased PD risk and the variable phenotypes observed in carriers of different GBA mutations are not yet fully elucidated. Extracellular vesicles (EVs) have gained increasing importance in neurodegenerative diseases since they can vehiculate pathological molecules potentially promoting disease propagation. Accumulating evidence showed that perturbations of the endosomal–lysosomal pathway can affect EV release and composition. Here, we investigate the impact of GCase deficiency on EV release and their effect in recipient cells. EVs were purified by ultracentrifugation from the supernatant of fibroblast cell lines derived from PD patients with or without GBA mutations and quantified by nanoparticle tracking analysis. SH-SY5Y cells over-expressing alpha-synuclein (α-syn) were used to assess the ability of patient-derived small EVs to affect α-syn expression. We observed that defective GCase activity promotes the release of EVs, independently of mutation severity. Moreover, small EVs released from PD fibroblasts carrying severe mutations increased the intra-cellular levels of phosphorylated α-syn. In summary, our work shows that the dysregulation of small EV trafficking and alpha-synuclein mishandling may play a role in GBA-associated PD.

Epigenetic regulation of SNCA gene expression in Parkinson’s disease

2020 ◽  
pp. 96-98
Author(s):  
А.К. Емельянов ◽  
А.О. Лавринова ◽  
Н.В. Мельникова ◽  
А.А. Дмитриев ◽  
И.В. Милюхина ◽  
...  
Keyword(s):  
Gene Expression ◽  
Peripheral Blood ◽  
Blood Cells ◽  
Cpg Island ◽  
Alpha Synuclein ◽  
Peripheral Blood Cells ◽  
Snca Gene ◽  
Intron 1 ◽  
And Control ◽  
First Time

В настоящем исследовании проведена оценка уровня мРНК и белка генов SNCA, DNMT1, а также степени метилирования интрона 1 гена SNCA в CD45+ клетках периферической крови пациентов со спорадической болезнью Паркинсона (БП) и индивидуумов контрольной группы. Впервые было выявлено снижение концентрации белка DNMT1 в CD45+ клетках периферической крови пациентов с БП по сравнению с группой контроля. Обнаружено увеличение уровня мРНК гена DNMT1 у пациентов с БП по сравнению с контролем. Не выявлено статистически значимых различий при сравнении степени метилирования интрона 1 гена SNCA в CD45+ клетках периферической крови пациентов с БП и контроля. В группе контроля выявлена обратная корреляция степени метилирования отдельных CpG островков с концентрацией белка альфа-синуклеина и уровнем мРНК гена SNCA. Проведенное исследование позволяет предположить участие гена DNMT1 в патогенезе БП и отсутствие ассоциации степени метилирования интрона 1 гена SNCA с БП. The aim of this study was to assess the level of mRNA and protein of the SNCA, DNMT1 genes, as well as intron 1 methylation of the SNCA gene in CD45 + peripheral blood cells of patients with sporadic PD and control individuals. For the first time, a decrease in the concentration of DNMT1 protein in CD45 + peripheral blood cells from PD patients compare to controls was revealed. An increase in DNMT1 gene expression in PD patients compare to controls was found. No differences in intron 1 methylation of the SNCA gene in CD45 + peripheral blood cells was found between PD patients and controls. An inverse correlations between methylation level of 21, 22 CpG island in intron1 of SNCA gene and mRNA SNCA gene and alpha-synuclein protein level were found. The study suggests the involvement of DNMT1 in the pathogenesis of PD and the lack of association of PD with intron 1 methylation of the SNCA gene.

REM sleep behavior disorder and other sleep abnormalities in p. A53T SNCA mutation carriers

SLEEP ◽  
2020 ◽  
Author(s):  
Athina Maria Simitsi ◽  
Christos Koros ◽  
Maria Stamelou ◽  
Dimitra Papadimitriou ◽  
Athanasios Leonardos ◽  
...  
Keyword(s):  
Sleep Disorder ◽  
Rem Sleep ◽  
Rem Sleep Behavior Disorder ◽  
Behavior Disorder ◽  
Alpha Synuclein ◽  
Sleep Behavior ◽  
Asymptomatic Carriers ◽  
Olfactory Testing ◽  
Obstructive Sleep ◽  
Sleep Abnormalities

Abstract Study Objectives Τo assess whether REM Sleep Behavior Disorder (RBD) and other sleep abnormalities occur in carriers of the p.A53T alpha-synuclein gene (SNCA) mutation, using both subjective and objective measures. Methods We have assessed 15 p.A53T carriers (10 manifesting Parkinson’s Disease [PD-A53T] and 5 asymptomatic carriers) with simultaneous Video-PSG (polysomnography) recording, the Epworth Sleepiness Scale (ESS) for daytime sleepiness, the Athens Insomnia Scale (AIS), the RBD Screening Questionnaire (RBDSQ) for clinical features of RBD, the Montreal Cognitive Assessment (MOCA) for cognition and the University of Pennsylvania Smell Identification Test (UPSIT) for olfaction. Results In our cohort, 90% of PD carriers had at least one sleep disorder and 40% had two: 4 RBD, 1 Periodic Limb Movements (PLM), 1 RBD plus PLM, 2 RBD plus moderate Obstructive Sleep Apnea (OSA), and 1 moderate OSA plus Restless Leg Syndrome. No asymptomatic carrier manifested a confirmed sleep disorder. 6/7 PD carriers with RBD had abnormal olfactory testing and 4/7 MOCA below cut off. There was a correlation of both impaired olfaction and cognition with RBD. Conclusions RBD occurs in the majority of PD-A53T, in contrast to most other genetic forms of PD, in which RBD is uncommon. The paucity of a sleep disorder in the asymptomatic carriers suggests that such carriers have not yet reached the prodromal phase when such sleep disorders manifest. Hyposmia in almost all subjects with RBD and cognitive decline in most of them are indicative of the general pattern of disease progression, which however is not uniform.

scholarly journals A small-angle X-ray scattering study of alpha-synuclein from human red blood cells

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Katsuya Araki ◽  
Naoto Yagi ◽  
Rie Nakatani ◽  
Hiroshi Sekiguchi ◽  
Masatomo So ◽  
...  
Keyword(s):  
Red Blood Cells ◽  
Small Angle ◽  
Blood Cells ◽  
Alpha Synuclein ◽  
X Ray ◽  
Human Red Blood Cells ◽  
X Ray Scattering ◽  
Scattering Study ◽  
Ray Scattering

Red Blood Cells Are the Major Source of Alpha-Synuclein in Blood

2008 ◽  
Vol 5 (2) ◽  
pp. 55-59 ◽  
Author(s):  
Robin Barbour ◽  
Kristin Kling ◽  
John P. Anderson ◽  
Kelly Banducci ◽  
Tracy Cole ◽  
...  
Keyword(s):  
Red Blood Cells ◽  
Blood Cells ◽  
Alpha Synuclein

Alpha-synuclein gene mRNA and protein level in cd45+ cells in patients with multiple systemic atrophy

2020 ◽  
pp. 101-102
Author(s):  
М.А. Николаев ◽  
Т.С. Усенко ◽  
А.И. Безрукова ◽  
Д.А. Богданова ◽  
К.А. Сенкевич ◽  
...  
Keyword(s):  
Blood Cells ◽  
Neurodegenerative Disorder ◽  
Early Stage ◽  
Alpha Synuclein ◽  
Peripheral Blood Cells ◽  
Diagnostic Biomarkers ◽  
Potential Biomarker ◽  
And Control ◽  
Multiple Systemic Atrophy ◽  
Gene Mrna

Множественная системная атрофия (МСА) - редкое нейродегенеративное заболевание, относящееся к группе заболеваний, ассоциированных с агрегацией белка альфа-синуклеина. Самой распространенной синуклеинопатией является болезнь Паркинсона (БП). Молекулярный механизм МСА и БП остается неизвестным, в связи с чем неизвестны диагностические биомаркеры, способные дифференцировать эти заболевания на ранней стадии. В данном исследовании был оценен уровень мРНК и белка альфа-синуклеина в CD45+ клетках периферической крови у пациентов с МСА, БП и в контроле. Выявленное значительное повышение экспрессии гена альфа-синуклеина у пациентов с МСА по сравнению с пациентами с БП (p<0,0001) и контрольной группой (p<0,0001). Уровень мРНК гена альфа-синуклеина CD45+ клеток крови может рассматриваться как потенциальный биомаркер МСА. Multiple system atrophy (MSA) is a rare neurodegenerative disorder that belongs to a group of neurodegenerative diseases called synucleinopathies. The most common synucleinopathy is Parkinson’s disease (PD). The molecular mechanism of MSA and PD remains unknown, and therefore diagnostic biomarkers that can differentiate these diseases at an early stage are unknown. The aim of this study was to estimate the level of mRNA and alpha-synuclein protein in CD45+ peripheral blood cells of patients with MSA, PD, and control. The significant increase of alpha-synuclein expression in MCA patients compared to patients with PD (p<0.0001) may be considered as a potential biomarker of this disease.

Sign in / Sign up

Export Citation Format

Share Document