Screening of GBA Mutations in Nigerian Patients with Parkinson's Disease

2021 ◽  
Author(s):  
Lukasz M. Milanowski ◽  
Olajumoke Oshinaike ◽  
Ronald L. Walton ◽  
Alexandra I. Soto‐Beasley ◽  
Rana Hanna Al‐Shaikh ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Gba Mutations

Clinical profiles associated with LRRK2 and GBA mutations in Brazilians with Parkinson's disease

2017 ◽  
Vol 381 ◽  
pp. 160-164 ◽  
Author(s):  
Camilla P. da Silva ◽  
Gabriella de M. Abreu ◽  
Pedro H. Cabello Acero ◽  
Mário Campos ◽  
João S. Pereira ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Profiles ◽  
Gba Mutations

scholarly journals Dermal fibroblasts from patients with Parkinson’s disease have normal GCase activity and autophagy compared to patients with PD and GBA mutations

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1751 ◽  
Author(s):  
Lucy M Collins ◽  
Janelle Drouin-Ouellet ◽  
Wei-Li Kuan ◽  
Timothy Cox ◽  
Roger A Barker
Keyword(s):  
Risk Factors ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Genetic Risk ◽  
Gaucher Disease ◽  
Dermal Fibroblasts ◽  
Skin Fibroblasts ◽  
Autophagic Flux ◽  
Clinical Progression ◽  
Gba Mutations

Background: Recently, the development of Parkinson’s disease (PD) has been linked to a number of genetic risk factors, of which the most common is glucocerebrosidase (GBA) mutations. Methods: We investigated PD and Gaucher Disease (GD) patient derived skin fibroblasts using biochemistry assays. Results: PD patient derived skin fibroblasts have normal glucocerebrosidase (GCase) activity, whilst patients with PD and GBA mutations have a selective deficit in GCase enzyme activity and impaired autophagic flux. Conclusions: This data suggests that only PD patients with a GBA mutation have altered GCase activity and autophagy, which may explain their more rapid clinical progression.

scholarly journals The Association between E326K of GBA and the Risk of Parkinson’s Disease

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Yongpan Huang ◽  
Langmei Deng ◽  
Yanjun Zhong ◽  
Minhan Yi
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Statistical Analysis ◽  
Subgroup Analysis ◽  
Gaucher Disease ◽  
Data Extraction ◽  
Meta Analysis ◽  
Minor Allele ◽  
Gba Mutations

It is reported that both the homozygous and heterozygous states of GBA mutations which are the causes of Gaucher disease (GD) are linked to the risk of PD. However, the GBA variant p.E326K (c.1093G > A, rs2230288), which does not result in GD in homozygous carriers, has triggered debate among experts studying Parkinson's disease (PD). In order to determine if the E326K variant of GBA is associated with the risk of PD, a standard meta-analysis was conducted by searching and screening publications, data extraction, and statistical analysis. Finally, a total of 15 publications, containing 5,908 PD patients and 5,605 controls, were included in this analysis. The pooled OR of the E326K genotype analysis was 1.99 (95% CI: 1.57–2.51). The minor allele frequencies of E326K for PD patients and controls were 1.67% and 1.03%, respectively. The pooled OR for the minor allele A was 1.99 (95% CI: 1.58–2.50). According to the subgroup analysis, we found that the significant differences between PD patients and controls for both genotype and allele of E326K also exist in Asians and Caucasians, respectively. In this study, we found that E326K of GBA is associated with the risk of PD in total populations, Asians, and Caucasians, respectively. Further studies are needed to clarify the role of GBA in the pathogenesis of PD.

Association of LRRK2 and GBA mutations in a Brazilian family with Parkinson's disease

2015 ◽  
Vol 21 (7) ◽  
pp. 825-826 ◽  
Author(s):  
Mariana Spitz ◽  
João Santos Pereira ◽  
Denise Hack Nicareta ◽  
Gabriella de Medeiros Abreu ◽  
Elenice Ferreira Bastos ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Gba Mutations

scholarly journals Risk Factors for Psychosis in Parkinson’s Disease

2017 ◽  
Vol 13 (02) ◽  
pp. 78
Author(s):  
Matthew J Barrett ◽  
Keyword(s):  
Risk Factors ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Visual Processing ◽  
Severe Disease ◽  
Executive Dysfunction ◽  
Neuropsychiatric Symptom ◽  
Increased Risk ◽  
Common Manifestation ◽  
Gba Mutations

Psychosis is a characteristic neuropsychiatric symptom of Parkinson’s disease (PD) that is common and associated with worse outcomes. The purpose of this article is to review identified risk factors for visual hallucinations in PD, the most common manifestation of psychosis. With the possible exception of dopamine agonists, antiparkinsonian medications are only considered modifiers of psychosis in PD. Dementia in PD has consistently been shown to be associated with psychosis, and executive dysfunction and impairment in visual processing appear to play a role in its pathogenesis. The association of psychosis with disorders of sleep–wake dysregulation and autonomic dysfunction supports the involvement of brainstem dysfunction in PD psychosis. Despite many studies evaluating genetic risk factors for hallucinations, GBA mutations are the only variants consistently reported to be associated with an increased risk of hallucinations in PD. Lastly, psychosis in PD is associated with a more severe disease burden, both related and unrelated to PD pathology. Any explanatory model of psychosis in PD must incorporate pharmacological, neuroanatomic, pathological, and genetic factors before there can be a complete understanding of this common and disabling neuropsychiatric symptom.

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.

Glucocerebrosidase Mutations and Motor Reserve in Parkinson’s Disease

2021 ◽  
pp. 1-10
Author(s):  
Seok Jong Chung ◽  
Phil Hyu Lee ◽  
Young H. Sohn ◽  
Yun Joong Kim
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rating Scale ◽  
Motor Deficits ◽  
Dopamine Depletion ◽  
Affected Side ◽  
Disease Rating ◽  
Individual Capacity ◽  
The Individual ◽  
Gba Mutations

Background: The concept of motor reserve explains the individual differences in motor deficits despite similar degrees of nigrostriatal dopamine depletion in Parkinson’s disease (PD). Objective: To investigate glucocerebrosidase (GBA) variants as potential determinants of motor reserve for exploratory purposes. Methods: A total of 408 patients with drug-naïve PD were enrolled from the Parkinson’s Progression Markers Initiative cohort database. All patients underwent SPECT dopamine transporter (DAT) scans and had results for Sanger sequencing of GBA. Parkinsonian motor deficits were assessed using the Movement Disorders Society Unified Parkinson’s Disease Rating Scale Part III (MDS-UPDRS-III). We compared MDS-UPDRS-III scores while adjusting for DAT availability in the putamen (i.e., motor reserve) between the PD groups according to the presence of GBA mutations. Results: Fifty-four (13.2%) patients carried GBA mutations. PD patients with GBA mutations were younger than those without mutations. There were no significant differences in sex, disease duration, years of education, and striatal DAT availability between the PD groups. PD patients with GBA mutations had higher MDS-UPDRS-III scores for the less affected side than those without mutations, despite similar levels of DAT availability in the contralateral putamen. The MDS-UPDRS-III sub-scores of the more affected side did not differ between the two PD groups. Conclusion: The results of this study demonstrated the detrimental effect of GBA variants on individual capacity to cope with PD-related pathologies, with different impacts depending on the motor laterality.

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