Deciphering the function of leucine-rich repeat kinase 2 and targeting its dysfunction in disease1

2012 ◽  
Vol 40 (5) ◽  
pp. 1039-1041 ◽  
Author(s):  
Patrick A. Lewis ◽  
Dario R. Alessi
Keyword(s):  
Parkinson’S Disease ◽  
Inflammatory Bowel Disease ◽  
Parkinson's Disease ◽  
Bowel Disease ◽  
Therapeutic Target ◽  
Unknown Function ◽  
Normal Function ◽  
Human Diseases ◽  
Leucine Rich Repeat ◽  
Inflammatory Bowel

LRRK2 (leucine-rich repeat kinase 2) is a gene of unknown function that has been linked to a number a human diseases, including PD (Parkinson's disease), IBD (inflammatory bowel disease), leprosy and cancer. The papers from the LRRK2: Function and Dysfunction meeting in this issue of Biochemical Society Transactions explore our growing knowledge of LRRK2's normal function, the role that it plays in disease and emerging strategies to exploit LRRK2 as a therapeutic target.

scholarly journals Inflammatory bowel disease and Parkinson’s disease: common pathophysiological links

Gut ◽  
2020 ◽  
pp. gutjnl-2020-322429 ◽  
Author(s):  
Ho-Su Lee ◽  
Evy Lobbestael ◽  
Séverine Vermeire ◽  
João Sabino ◽  
Isabelle Cleynen
Keyword(s):  
Parkinson’S Disease ◽  
Inflammatory Bowel Disease ◽  
Parkinson's Disease ◽  
Bowel Disease ◽  
Population Based ◽  
Leucine Rich Repeat ◽  
Causal Gene ◽  
Genetic Studies ◽  
Inflammatory Bowel ◽  
Shared Genetic

Inflammatory bowel disease and Parkinson’s disease are chronic progressive disorders that mainly affect different organs: the gut and brain, respectively. Accumulating evidence has suggested a bidirectional link between gastrointestinal inflammation and neurodegeneration, in accordance with the concept of the ‘gut–brain axis’. Moreover, recent population-based studies have shown that inflammatory bowel disease might increase the risk of Parkinson's disease. Although the precise mechanisms underlying gut–brain interactions remain elusive, some of the latest findings have begun to explain the link. Several genetic loci are shared between both disorders with a similar direction of effect on the risk of both diseases. The most interesting example is LRRK2 (leucine-rich repeat kinase 2), initially identified as a causal gene in Parkinson's disease, and recently also implicated in Crohn’s disease. In this review, we highlight recent findings on the link between these seemingly unrelated diseases with shared genetic susceptibility. We discuss supporting and conflicting data obtained from epidemiological and genetic studies along with remaining questions and concerns. In addition, we discuss possible biological links including the gut–brain axis, microbiota, autoimmunity, mitochondrial function and autophagy.

scholarly journals Immunomodulatory role of Parkinson’s disease 7 in inflammatory bowel disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rita Lippai ◽  
Apor Veres-Székely ◽  
Erna Sziksz ◽  
Yoichiro Iwakura ◽  
Domonkos Pap ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Inflammatory Bowel Disease ◽  
Parkinson's Disease ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Tnf Α ◽  
Inflammatory Bowel ◽  
Ht 29

AbstractRecently the role of Parkinson’s disease 7 (PARK7) was studied in gastrointestinal diseases, however, the complex role of PARK7 in the intestinal inflammation is still not completely clear. Expression and localization of PARK7 were determined in the colon biopsies of children with inflammatory bowel disease (IBD), in the colon of dextran sodium sulphate (DSS) treated mice and in HT-29 colonic epithelial cells treated with interleukin (IL)-17, hydrogen peroxide (H2O2), tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β or lipopolysaccharide (LPS). Effect of PARK7 on the synthesis of IBD related cytokines was determined using PARK7 gene silenced HT-29 cells and 3,4,5-trimethoxy-N-(4-(8-methylimidazo(1,2-a)pyridine-2-yl)phenyl)benzamide (Comp23)—compound increasing PARK7 activity—treated mice with DSS-colitis. PARK7 expression was higher in the mucosa of children with Crohn’s disease compared to that of controls. While H2O2 and IL-17 treatment increased, LPS, TNF-α or TGF-β treatment decreased the PARK7 synthesis of HT-29 cells. PARK7 gene silencing influenced the synthesis of IL1B, IL6, TNFA and TGFB1 in vitro. Comp23 treatment attenuated the ex vivo permeability of colonic sacs, the clinical symptoms, and mucosal expression of Tgfb1, Il1b, Il6 and Il10 of DSS-treated mice. Our study revealed the role of PARK7 in the regulation of IBD-related inflammation in vitro and in vivo, suggesting its importance as a future therapeutic target.

scholarly journals Is Parkinson’s disease a chronic low-grade inflammatory bowel disease?

2019 ◽  
Vol 267 (8) ◽  
pp. 2207-2213 ◽  
Author(s):  
Malvyne Rolli-Derkinderen ◽  
Laurène Leclair-Visonneau ◽  
Arnaud Bourreille ◽  
Emmanuel Coron ◽  
Michel Neunlist ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Inflammatory Bowel Disease ◽  
Parkinson's Disease ◽  
Bowel Disease ◽  
Low Grade ◽  
Inflammatory Bowel

scholarly journals The Impact of Korean Medicine Treatment on the Incidence of Parkinson’s Disease in Patients with Inflammatory Bowel Disease: A Nationwide Population-Based Cohort Study in South Korea

2020 ◽  
Vol 9 (8) ◽  
pp. 2422 ◽  
Author(s):  
Hyeonseok Noh ◽  
Jeongju Jang ◽  
Seungwon Kwon ◽  
Seung-Yeon Cho ◽  
Woo-Sang Jung ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Inflammatory Bowel Disease ◽  
Parkinson's Disease ◽  
South Korea ◽  
Bowel Disease ◽  
Therapy Group ◽  
Monotherapy Group ◽  
Korean Medicine ◽  
Integrative Therapy ◽  
Inflammatory Bowel

We aimed to investigate the association between Korean medicine (KM) treatment and the risk of Parkinson’s Disease (PD) in patients with inflammatory bowel disease (IBD) in South Korea. This study analyzed data from the National Health Insurance Service-Senior cohort in South Korea. The 1816 IBD patients enrolled in the analysis comprised 411 who received only conventional treatment (monotherapy group) and 1405 who received both conventional and KM treatments (integrative therapy group). The risk of PD in patients with IBD was significantly lower in the integrative therapy group than in the monotherapy group after adjusting for confounding variables (adjusted hazard ratio (HR), 0.56; 95% confidence interval (CI) = 0.34–0.92). In the mild Charlson Comorbidity Index (CCI) group, the risk of PD in patients with IBD in the integrative therapy group was 0.39 times lower (adjusted HR, 95% CI = 0.20–0.77) than that in the monotherapy group. However, there was no significant difference in the risk of PD in patients with IBD between the integrative therapy and monotherapy groups among individuals with severe CCI (adjusted HR, 0.90; 95% CI = 0.41−1.96). IBD patients are at a decreased risk of PD when they receive integrative therapy. KM treatment may prevent PD in IBD patients.

Association between inflammatory bowel disease and Parkinson’s disease: seek and you shall find?

Gut ◽  
2018 ◽  
Vol 68 (1) ◽  
pp. 175-176 ◽  
Author(s):  
Petra Weimers ◽  
Jonas Halfvarson ◽  
Michael C Sachs ◽  
Jonas F Ludvigsson ◽  
Inga Peter ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Inflammatory Bowel Disease ◽  
Parkinson's Disease ◽  
Bowel Disease ◽  
Inflammatory Bowel
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