Alteration of Phospholipase C-δ Protein Level and Specific Activity in Alzheimer's Disease

2002 ◽  
Vol 64 (6) ◽  
pp. 2629-2634 ◽  
Author(s):  
Shun Shimohama ◽  
Sadaki Fujimoto ◽  
Hideyuki Matsushima ◽  
Tadafumi Takenawa ◽  
Takashi Taniguchi ◽  
...  
1995 ◽  
Vol 16 (6) ◽  
pp. 895-900 ◽  
Author(s):  
Hideyuki Matsushima ◽  
Shun Shimohama ◽  
Sadaki Fujimoto ◽  
Tadafumi Takenawa ◽  
Jun Kimura

2018 ◽  
Vol 15 (7) ◽  
pp. 610-617 ◽  
Author(s):  
Huifeng Zhang ◽  
Dan Liu ◽  
Huanhuan Huang ◽  
Yujia Zhao ◽  
Hui Zhou

Background: β-amyloid (Aβ) accumulates abnormally to senile plaque which is the initiator of Alzheimer's disease (AD). As one of the Aβ-degrading enzymes, Insulin-degrading enzyme (IDE) remains controversial for its protein level and activity in Alzheimer's brain. Methods: The electronic databases PubMed, EMBASE, The Cochrane Library, OVID and Sinomed were systemically searched up to Sep. 20th, 2017. And the published case-control or cohort studies were retrieved to perform the meta-analysis. Results: Seven studies for IDE protein level (AD cases = 293; controls = 126), three for mRNA level (AD cases = 138; controls = 81), and three for enzyme activity (AD cases = 123; controls = 75) were pooling together. The IDE protein level was significantly lower in AD cases than in controls (SMD = - 0.47, 95% CI [-0.69, -0.24], p < 0.001), but IDE mRNA and enzyme activity had no significant difference (SMD = 0.02, 95% CI [-0.40, 0.43] and SMD = 0.06, 95% CI [-0.41, 0.53] respectively). Subgroup analyses found that IDE protein level was decreased in both cortex and hippocampus of AD cases (SMD = -0.43, 95% CI [-0.71, -0.16], p = 0.002 and SMD = -0.53, 95% CI [-0.91, -0.15], p = 0.006 respectively). However, IDE mRNA was higher in cortex of AD cases (SMD = 0.71, 95% CI [0.14, 1.29], p = 0.01), not in hippocampus (SMD = -0.26, 95% CI [-0.58, 0.06]). Conclusions: Our results indicate that AD patients may have lower IDE protease level. Further relevant studies are still needed to verify whether IDE is one of the factors affecting Aβ abnormal accumulation and throw new insights for AD detection or therapy.


2016 ◽  
Vol 50 (4) ◽  
pp. 1181-1189 ◽  
Author(s):  
Mariacristina Siotto ◽  
Ilaria Simonelli ◽  
Patrizio Pasqualetti ◽  
Stefania Mariani ◽  
Deborah Caprara ◽  
...  

1998 ◽  
Vol 92 (5-6) ◽  
pp. 509-510
Author(s):  
A. Wevers ◽  
S. Nowacki ◽  
J. Lindstrom ◽  
U. Schütz ◽  
E. Giacobini ◽  
...  

2012 ◽  
Vol 4 (1-2) ◽  
pp. 48-50 ◽  
Author(s):  
Yu-Fen Lin ◽  
Ming-Hui Yang ◽  
Yuan-Han Yang ◽  
Wen-Cheng Chen ◽  
Chi-Yu Lu ◽  
...  

2018 ◽  
Author(s):  
Lorenza Magno ◽  
Christian B Lessard ◽  
Marta Martins ◽  
Pedro Cruz ◽  
Matilda Katan ◽  
...  

ABSTRACTRecent Genome Wide Association Studies (GWAS) have identified novel rare coding variants in immune genes associated with late onset AD (LOAD). Amongst these, a polymorphism in Phospholipase C-gamma 2 (PLCG2) P522R, has been reported to be protective against LOAD. PLC enzymes are key elements in signal transmission networks and are potentially druggable targets. PLCG2 is highly expressed in the hematopoietic system. Hypermorphic mutations in PLCG2 in humans have been reported to cause autoinflammation and immune disorders, suggesting a key role for this enzyme in the regulation of immune cell function.We confirmed that PLCG2 expression is restricted primarily to microglia in both the healthy and AD brain. Functional analysis of the P522R variant in heterologous systems demonstrated a small hypermorphic effect of the mutation on enzyme function. PLCγ2 is therefore a potential target for modulating microglia function in AD, and a small molecule drug that weakly activates PLCγ2 may be one potential therapeutic approach.SUMMARYThe PLCG2 P522R variant is protective against Alzheimer’s disease (AD). We show that PLCG2 is expressed in CNS-resident myeloid cells, and the P522R polymorphism weakly activates enzyme function. These data suggest that activation of PLCG2 and not inhibition could be therapeutically beneficial in AD.


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