scholarly journals Blockade of enzyme activity inhibits tissue transglutaminase-mediated transamidation of α-synuclein in a cellular model of Parkinson's disease

2011 ◽  
Vol 58 (7) ◽  
pp. 785-793 ◽  
Author(s):  
Robin Verhaar ◽  
Cornelis A.M. Jongenelen ◽  
Melanie Gerard ◽  
Veerle Baekelandt ◽  
Anne-Marie Van Dam ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Enzyme Activity ◽  
Tissue Transglutaminase ◽  
Cellular Model

Increase in endoplasmic reticulum-associated tissue transglutaminase and enzymatic activation in a cellular model of Parkinson's disease

2012 ◽  
Vol 45 (3) ◽  
pp. 839-850 ◽  
Author(s):  
Robin Verhaar ◽  
Benjamin Drukarch ◽  
John G.J.M. Bol ◽  
Cornelis A.M. Jongenelen ◽  
René J.P. Musters ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Endoplasmic Reticulum ◽  
Tissue Transglutaminase ◽  
Cellular Model ◽  
Enzymatic Activation

scholarly journals Fibroblasts from idiopathic Parkinson’s disease exhibit deficiency of lysosomal glucocerebrosidase activity associated with reduced levels of the trafficking receptor LIMP2

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Ria Thomas ◽  
Elizabeth B. Moloney ◽  
Zachary K. Macbain ◽  
Penelope J. Hallett ◽  
Ole Isacson
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Enzyme Activity ◽  
Current Data ◽  
Lysosomal Hydrolase ◽  
Protein Levels ◽  
Control Subjects ◽  
Er Retention ◽  
Trafficking Receptor ◽  
N370s Mutation

AbstractLysosomal dysfunction is a central pathway associated with Parkinson’s disease (PD) pathogenesis. Haploinsufficiency of the lysosomal hydrolase GBA (encoding glucocerebrosidase (GCase)) is one of the largest genetic risk factors for developing PD. Deficiencies in the activity of the GCase enzyme have been observed in human tissues from both genetic (harboring mutations in the GBA gene) and idiopathic forms of the disease. To understand the mechanisms behind the deficits of lysosomal GCase enzyme activity in idiopathic PD, this study utilized a large cohort of fibroblast cells from control subjects and PD patients with and without mutations in the GBA gene (N370S mutation) (control, n = 15; idiopathic PD, n = 31; PD with GBA N370S mutation, n = 6). The current data demonstrates that idiopathic PD fibroblasts devoid of any mutations in the GBA gene also exhibit reduction in lysosomal GCase activity, similar to those with the GBA N370S mutation. This reduced GCase enzyme activity in idiopathic PD cells was accompanied by decreased expression of the GBA trafficking receptor, LIMP2, and increased ER retention of the GBA protein in these cells. Importantly, in idiopathic PD fibroblasts LIMP2 protein levels correlated significantly with GCase activity, which was not the case in control subjects or in genetic PD GBA N370S cells. In conclusion, idiopathic PD fibroblasts have decreased GCase activity primarily driven by altered LIMP2-mediated transport of GBA to lysosome and the reduced GCase activity exhibited by  the genetic GBA N370S derived PD fibroblasts occurs through a different mechanism.

scholarly journals Mechanisms of DJ-1 neuroprotection in a cellular model of Parkinson’s disease

2008 ◽  
Vol 105 (6) ◽  
pp. 2435-2453 ◽  
Author(s):  
Fang Liu ◽  
Jamie L. Nguyen ◽  
John D. Hulleman ◽  
Li Li ◽  
Jean-Christophe Rochet
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cellular Model

Neuroprotective Effects of the Small-Molecule Enhancer of Rapamycin in the Cellular Model of Parkinson’s Disease

2019 ◽  
Vol 51 (2) ◽  
pp. 88-96
Author(s):  
S. Darabi ◽  
A. Noori-Zadeh ◽  
F. Rajaei ◽  
H. A. Abbaszadeh ◽  
M.-A. Abdollahifar ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Small Molecule ◽  
Cellular Model ◽  
Neuroprotective Effects
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