Recombinant Human Lysosomal acid glucosylceramidase (GBA1) (N409S)

1. Chinese type 2 Gaucher disease patients have a similar phenotype to other ethnic groups and have a high prevalence of the c.1448T>C (p.Leu483Pro) mutation and recombination alleles. PMID: 29934114
2. The binding affinities of a-1-C-alkyl 1,4-dideoxy-1,4-imino-d-arabinitol (DAB) derivatives, which act as pharmacological chaperones for beta-glucocerebrosidase, abruptly increased upon elongation of their alkyl chain. In this study, the primary causes of such an increase in binding affinity were analyzed using proteinligand docking and molecular dynamics simulations. PMID: 30340368
3. The POLG1 CAG repeat length variation and the GBA p.L444P variant are associated with Parkinson's disease in the Finnish population PMID: 29029963
4. that GBA variant E326K may fully account for the primary association signal observed at chromosome 1q22 in previous GWAS of PD PMID: 28830825
5. lipid dyshomeostasis by GBA1 deficiency leads to decreased alpha-synuclein tetramers and increased alpha-synuclein monomers, which may provide the building blocks for phospho-Ser129-positive aggregates in GBA1-Parkinson's disease induced pluripotent stem cell-derived dopaminergic neurons PMID: 29311330
6. This study found that 10/13 Parkinson's disease parents had a severe mutation and only 3/10 carried a mild mutation (binomial test P < 0.05). Using an unbiased methodology, this study showed that carriers of severe GBA mutations are at higher risk for Parkinson's disease relative to carriers of the mild mutations. PMID: 27864021
7. The mutation spectrum of GBA exhibits ethnic and regional disparity in Asian patients. L444P was the most frequent mutation accounted for 47.7% in southern Chinese patients. The L444P homozygote genotype was associated with severe type 1 Gaucher disease. PMID: 27865684
8. These results indicated activation of Unfolded Protein Response (UPR) in different cell types derived from Gaucher disease patients, highlighting the generality of this process in this disease. They also showed that the UPR-regulated CHOP transcription factor induces transcription of the GBA1 gene. PMID: 27856178
9. The aims in the present study were to validate the P338-X1 GBA kit (MRC-Holland) for Multiplex Ligation-dependent Probe Amplification (MLPA) and to detect large deletions and/or duplications in GBA1 in Gaucher disease (GD) patients from Southern Brazil. Although larger deletions/duplications do not appear to be frequent in GD, the P338-X1 GBA kit for MLPA appears to be a good method for GBA1 analysis. PMID: 27825739
10. The data of this study suggested that the prominent cognitive impairment in Glucocerebrosidase (GBA)-associated Parkinson disease seems not primarily associated with specific Abeta and Tau profiles in CSF. PMID: 29094781
11. This study demonstrated that GBA status appears to be an important predictor for non-motor symptom disease progression, after deep brain stimulation surgery. PMID: 28777757
12. The results of this study support a connection between the loss of beta-glucocerebrosidase-1 function, cholesterol accumulation, and the disruption of cellular homeostasis in GBA1-PD. PMID: 28779532
13. comparative analysis of motor and non-motor features in LRRK2 and GBA mutation carriers and non-carriers conducted in a cohort from Brazil, a country with a highly miscegenated population. Similarly to other studies, our results suggest that mutations in GBA and LRRK2 influence the clinical signs of the Parkinson's disease, with significant implications for handling of specific patient groups. PMID: 28991672
14. This study showed that Lysosomal defects GBA associated familial Parkinson's disease. PMID: 28894968
15. In longitudinally assessed, autopsied Parkinson disease cases, those with GBA mutations had a younger age at death but there was no evidence for clinical or neuropathological differences compared to cases without GBA mutations. PMID: 28834018
16. Low Glucosylceramidase serum levels are associated with Gaucher disease. PMID: 28356566
17. these findings highlight the critical role of GBA1 in mediating enhanced self-consumption of intracellular components and endomembranes, leading to autophagic cell death. PMID: 28574511
18. examined the effect of heterozygous mutation status on 736 community-dwelling older adults without dementia or Parkinson's disease over an average of 6 years, 28 of whom had a single GBA mutation (primarily N370S); carriers showed greater decline in verbal memory over time;results suggest an effect, but an overall limited burden, of harboring a single GBA mutation in aging mutation carriers PMID: 28728889
19. dose effect of mutations in the GBA gene on Parkinson's disease phenotype; severity of Parkinson's disease phenotype is related to the burden of GBA mutations with Gaucher disease-Parkinson's disease patients manifesting a more severe phenotype PMID: 28012950
20. This study shown GBA genetic variants for Parkinson's disease are associated with the risk of incident Parkinson's disease in the general population and with impairment in daily functioning in individuals without clinical parkinsonism. PMID: 27269966
21. This study showed that GBA L444P and SNCA Rep-1 were also associated with depression in Parkinson's disease. PMID: 27745782
22. Parkinson's disease is associated with mutations in GBA. Ashkenazi Jews GBA carriers were singled at a significantly earlier age at diagnosis compared to noncarriers. PMID: 27449028
23. GBA mutations are also an important risk factor for DLB development in the Spanish population, are associated with earlier disease onset, and are more prevalent in men. PMID: 27027900
24. These results demonstrate the diagnostic usefulness of MLPA in the detection of GBA deletions and recombinations PMID: 27802905
25. A novel function for glucocerebrosidase as a regulator of sterylglucoside metabolism has been summarized. (Review) PMID: 28596107
26. Mutant GBA proteins cause increases in alpha-synuclein levels, while an inhibition of GBA by alpha-synuclein has been also demonstrated in Gaucher disease patients with Parkinson disease. (Review) PMID: 26965692
27. GBA mutations as risk factors for PD and point to lysosomal dysfunction as a mechanism contributing to PD etiology. PMID: 27255555
28. Parkinson patient who carry mutations in the GBA gene demonstrates more significant cognitive decline compared to idiopathic parkinson patients. PMID: 27401793
29. Mesenchymal stem cells with reduced GBA activity are prone to apoptosis and senescence due to impaired autophagy and DNA repair capacity. PMID: 28098348
30. Local lysosomal conditions may be even more critical for some mutant lysosomal hydrolases, e.g. for mutant GBA1 . In Niemann-Pick disease type C disease, characterized by the cholesterol primary storage, GlcCer secondary accumulation could be triggered by SM secondary accumulation. PMID: 28126847
31. the GBA1 gene, its role in Gaucher disease, and its link with Parkinson disease (Review) PMID: 26860875
32. the decrease in enzymatic activity of lysosomal hydrolases in GBA mutation carriers may contribute to Parkinson disease pathogenesis by increasing the level of neurotoxic oligomeric alpha-synuclein species. PMID: 27780739
33. the important contribution of GBA (L444P and N370S) mutations to parkinsonism in Brazilian families. PMID: 27777137
34. In a Flanders-Belgian cohort, carrier status of a heterozygous glucocerebrosidase (GBA) mutation was a strong genetic risk factor for Parkinson's disease (PD). The GBA mutation frequency of 4.5% is comparable to previously reported data in other European PD patient cohorts. PMID: 27397011
35. Rab7 accumulated in GCase deficient cells, supporting the notion that lysosomal recycling is impaired. Since recombinant GCase can reverse ALR impairment, we anticipate that strategies to restore GCase activity in the brains of both sporadic patients with PD and those with GBA1 mutations will improve autophagy lysosomal pathway, preventing the accumulation of a-synuclein and spread of pathology. PMID: 27378698
36. course of motor and non-motor symptoms as well as treatment-related motor complications could be influenced by GBA variants PMID: 28030538
37. The anti-enterovirus 71 activity of GBA1 was bimodal: endogenous GBA1 restricted cell surface expression levels of scavenger receptor class B, member 2 (SCARB2), also known as lysosomal integral membrane protein 2 (LIMP-2), and exogenous recombinant GBA1 interfered with enterovirus 71 to interact with SCARB2 outside the cell. PMID: 28141506
38. identified the significant associations of the GBA L444P mutation and DYRK1A rs8126696 T allele with the earlier age at onset (AAO) in Parkinson's disease (PD) patients, and the A allele at MS4A6A rs610932 with the delayed AAO of PD. PMID: 27085534
39. Results suggest that GBA1 mutations confer greater risk of neuropsychiatric morbidity in Parkinson disease, and that sex may affect this association PMID: 27772789
40. Although a common ancestry among Southern Italian and Swedish Norrbottnian GD patients could not be investigated, the beta glucosidase genotype [L444P]+[L444P] is the most frequently encountered in Southern Italy PMID: 28003644
41. Mutations in the GBA gene pathogenic for neuropathic GD and complex alleles shift longitudinal cognitive decline in PD into "high gear." PMID: 27717005
42. In the clinical continuum between PD and DLB, patients with GBA mutations seem to localize midway, with carriers of severe mutations closer to DLB than to idiopathic PD. PMID: 27632223
43. GBA variants predict a more rapid progression of cognitive dysfunction and motor symptoms in patients with Parkinson's. PMID: 27571329
44. Mutations in the GBA gene were associated with more severe motor and cognitive dysfunction, supporting a specific contribution of the GBA gene or lysosome function in Lewy body disease among Ashkenazi Jews. PMID: 27723861
45. GBA enzyme activity in Parkinson disease patients was lower in GBA mutation carriers vs. non-GBA carriers. PMID: 26857292
46. Combination of chemo drug with beta-glucosidase 1 inhibitor sensitized hepatocellular carcinoma (HCC) cells to chemotherapy. Our data support b-glucosidase 1 as a HCC biomarker due to its prognosis significance PMID: 26849828
47. the study supported that GBA mutations were a risk factor for Parkinson's disease in the European population PMID: 26868973
48. The clinical phenotype of GBA-associated neurodegenerative disease is more heterogeneous than previously assumed, including phenotypes not usually associated with underlying alpha-synucleinopathies. PMID: 26549049
49. there has been a boom in studies investigating the role of glucocerebrosidase in the pathology of Parkinson's disease. This merits a comprehensive review of the current cell biological processes and pathological pictures involving Parkinson's disease associated with GBA mutations PMID: 26743617
50. GBA mutations were found to be a common genetic risk factor for Parkinson disease in Eastern Canadian patients. PMID: 26000814

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HGNC: 4177

OMIM: 168600

KEGG: hsa:2629

STRING: 9606.ENSP00000314508

UniGene: Hs.282997