Correction: Insights into the genetic epidemiology of Crohn's and rare diseases in the Ashkenazi Jewish population

Rivas, Manuel A.; Avila, Brandon E.; Koskela, Jukka; Huang, Hailiang; Stevens, Christine; Pirinen, Matti; Haritunians, Talin; Neale, Benjamin M.; Kurki, Mitja; Ganna, Andrea; Graham, Daniel B.; Gläser, Benjamin; Peter, Inga; Atzmon, Gil; Barzilai, Nir; Levine, Adam P.; Schiff, Elena; Pontikos, Nikolas; Weisburd, Ben; Lek, Monkol; Karczewski, Konrad J.; Bloom, Jonathan M.; Minikel, Eric Vallabh; Petersen, Britt‐Sabina; Beaugerie, Laurent; Seksik, Philippe; Cosnes, Jacques; Schreiber, Stefan; Bokemeyer, Bernd; Bethge, Johannes; Heap, Graham A.; Ahmad, Tariq; Plagnol, Vincent; Segal, Anthony W.; Targan, Stephan; Turner, Dan; Saavalainen, Päivi; Färkkilä, M.; Kontula, Kimmo; Palotie, Aarno; Brant, Steven R.; Duerr, Richard H.; Silverberg, Mark S.; Rioux, John D.; Weersma, Rinse K.; Franke, André; Jostins, Luke; Anderson, Carl A.; Barrett, Jeffrey C.; MacArthur, Daniel G.; Jalas, Chaim; Sokol, Harry; Xavier, Ramnik J.; Pulver, Ann E.; Cho, Judy H.; McGovern, Dermot P.; Daly, Mark J.

doi:10.1371/journal.pgen.1008190

Cited by 4 publications

(3 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, it is well established that mutations in the LRRK2 gene increase risk of developing PD in patients with Crohn's disease 10 or ulcerative colitis 190 . Furthermore, LRRK2 has been identified by GWAS as a major susceptibility gene for Crohn's disease 190 , and the PD-associated G2019S mutation contributed genetic risk for Crohn's disease 11,191 . Collectively, autoimmune diseases represent a group of disorders in which the peripheral immune system is chronically activated and producing inflammatory mediators that may stimulate neuroinflammation and thereby promote PD pathogenesis.…”

Section: Epidemiological Evidencementioning

confidence: 99%

Inflammation and immune dysfunction in Parkinson disease

et al. 2022

View full text Add to dashboard Cite

Parkinson disease (PD) is a progressive neurodegenerative disease that affects peripheral organs as well as the central nervous system and involves a fundamental role of neuroinflammation in its pathophysiology. Neurohistological and neuroimaging studies support the presence of ongoing and end-stage neuroinflammatory processes in PD. Moreover, numerous studies of peripheral blood and cerebrospinal fluid from patients with PD suggest alterations in markers of inflammation and immune cell populations that could initiate or exacerbate neuroinflammation and perpetuate the neurodegenerative process. A number of disease genes and risk factors have been identified as modulators of immune function in PD and evidence is mounting for a role of viral or bacterial exposure, pesticides and alterations in gut microbiota in disease pathogenesis. This has led to the hypothesis that complex gene-by-environment interactions combine with an ageing immune system to create the 'perfect storm' that enables the development and progression of PD. We discuss the evidence for this hypothesis and opportunities to harness the emerging immunological knowledge from patients with PD to create better preclinical models with the long-term goal of enabling earlier identification of at-risk individuals to prevent, delay and more effectively treat the disease.

show abstract

Section: Epidemiological Evidencementioning

confidence: 99%

Inflammation and immune dysfunction in Parkinson disease

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Interestingly, the protective variant R1398H was shown to increase GTPase activity, deactivating LRRK2. Furthermore, the PD-associated G2019S mutation has been shown to be increased in CD patients in the Ashkenazi Jewish population (Rivas et al, 2019). It is evident therefore that LRRK2 is associated with both PD and IBD, and increased LRRK2 activity may increase susceptibility to inflammation of the gastrointestinal tract which may play a role in PD.…”

Section: Lrrk2 and The Gut-brain Axismentioning

confidence: 99%

LRRK2 at the Interface Between Peripheral and Central Immune Function in Parkinson’s

2020

View full text Add to dashboard Cite

It is becoming increasingly accepted that there is an interplay between the peripheral immune response and neuroinflammation in the pathophysiology of Parkinson's disease (PD). Mutations in the leucine-rich-repeat kinase 2 (LRRK2) gene are associated with familial and sporadic cases of PD but are also found in immune-related disorders, such as inflammatory bowel disease (IBD) and leprosy. Furthermore, LRRK2 has been associated with bacterial infections such as Mycobacterium tuberculosis and Salmonella typhimurium. Recent evidence suggests a role of LRRK2 in the regulation of the immune system and modulation of inflammatory responses, at a systemic level, with LRRK2 functionally implicated in both the immune system of the central nervous system (CNS) and the periphery. It has therefore been suggested that peripheral immune signaling may play an important role in the regulation of neurodegeneration in LRRK2 as well as non-LRRK2-associated PD. This review will discuss the current evidence for this hypothesis and will provide compelling rationale for placing LRRK2 at the interface between peripheral immune responses and neuroinflammation.

show abstract

“…LRRK2 has been identified by GWAS as a major susceptibility gene for CD [53], and the gain-of-function variant, N2081D , has recently been identified and shown to increase the risk of CD two-fold in at-risk populations [27]. The G2019S mutation, which increases kinase activity, has been shown to be increased in CD patients in the Ashkenazi Jewish population [28]. Furthermore, the down-regulation of LRRK2 was previously shown to enhance the susceptibility to dextran sulfate sodium salt (DSS)-induced colitis [22], suggesting a loss of LRRK2 activity may increase the risk for inflammation in the gut.…”

Section: Lrrk2 Kinase Activity In Diseasementioning

confidence: 99%

LRRK2 regulation of immune-pathways and inflammatory disease

Wallings

Tansey

2019

Biochemical Society Transactions

112

View full text Add to dashboard Cite

Mutations in the leucine-rich-repeat kinase 2 (LRRK2) gene are associated with familial and sporadic cases of Parkinson's disease but are also found in immune-related disorders such as inflammatory bowel disease, tuberculosis and leprosy. LRRK2 is highly expressed in immune cells and has been functionally linked to pathways pertinent to immune cell function, such as cytokine release, autophagy and phagocytosis. Here, we examine the current understanding of the role of LRRK2 kinase activity in pathway regulation in immune cells, drawing upon data from multiple diseases associated with LRRK2 to highlight the pleiotropic effects of LRRK2 in different cell types. We discuss the role of the bona fide LRRK2 substrate, Rab GTPases, in LRRK2 pathway regulation as well as downstream events in the autophagy and inflammatory pathways.

show abstract

Correction: Insights into the genetic epidemiology of Crohn's and rare diseases in the Ashkenazi Jewish population

Cited by 4 publications

References 1 publication

Inflammation and immune dysfunction in Parkinson disease

Inflammation and immune dysfunction in Parkinson disease

LRRK2 at the Interface Between Peripheral and Central Immune Function in Parkinson’s

LRRK2 regulation of immune-pathways and inflammatory disease

Contact Info

Product

Resources

About