<i>LRRK2</i>G2019S as a Cause of Parkinson's Disease in Ashkenazi Jews

Ozelius, Laurie J.; Senthil, Geetha; Saunders‐Pullman, Rachel; Ohmann, Erin; Deligtisch, Amanda; Tagliati, Michele; Hunt, Amelia R.; Klein, Christine; Henick, Brian S.; Hailpern, Susan M.; Lipton, Richard B.; Soto-Valencia, Jeannie; Risch, Neil; Bressman, Susan

doi:10.1056/nejmc055509

Cited by 642 publications

(502 citation statements)

References 8 publications

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“…The frequency of the most common mutation, G2019S, varies across populations, is most common in North African and Jewish populations [210,213], while it seems to be rare in Asian [214,215] and South African populations [216]. Studies that examined the origin of the mutation by haplotype analyses reported only three haplotypes, indicating founder effects [212].…”

Section: Lrrk2 (Park8)mentioning

confidence: 99%

Epidemiology and etiology of Parkinson’s disease: a review of the evidence

et al. 2011

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Section: Lrrk2 (Park8)mentioning

confidence: 99%

Epidemiology and etiology of Parkinson’s disease: a review of the evidence

et al. 2011

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“…Although most monogenic mutations account for only a very small proportion of the PD population, the mutation of specific genes like LRRK2 may be associated with as much as 30% of PD patients in some populations like Ashkenazi Jews (Ozelius et al, 2006;Saunders-Pullman et al, 2006;Cookson, 2010;Dachsel and Farrer, 2010). Some imaging studies have demonstrated abnormal dopaminergic function in the striatum in small groups of patients with LRRK2 or other Park gene mutations (Khan et al, 2002;Adams et al, 2005).…”

Section: Neuroimagingmentioning

confidence: 99%

Parkinson's Disease Therapeutics: New Developments and Challenges Since the Introduction of Levodopa

Smith

Wichmann

Factor

et al. 2011

Neuropsychopharmacol

194

137

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The demonstration that dopamine loss is the key pathological feature of Parkinson's disease (PD), and the subsequent introduction of levodopa have revolutionalized the field of PD therapeutics. This review will discuss the significant progress that has been made in the development of new pharmacological and surgical tools to treat PD motor symptoms since this major breakthrough in the 1960s. However, we will also highlight some of the challenges the field of PD therapeutics has been struggling with during the past decades. The lack of neuroprotective therapies and the limited treatment strategies for the nonmotor symptoms of the disease (ie, cognitive impairments, autonomic dysfunctions, psychiatric disorders, etc.) are among the most pressing issues to be addressed in the years to come. It appears that the combination of early PD nonmotor symptoms with imaging of the nigrostriatal dopaminergic system offers a promising path toward the identification of PD biomarkers, which, once characterized, will set the stage for efficient use of neuroprotective agents that could slow down and alter the course of the disease.

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“…The most frequent mutation, Lrrk2 G2019S, originates from a common founder [4], presents with age-dependent penetrance and is responsible for 0.5-2.0% of cases of sporadic PD and 5% of familial parkinsonism in Caucasians [9,10]. Remarkably, it accounts for 29% of Ashkenazi Jews and 37% of North African Arabs with familial parkinsonism and for 13 and 30%, respectively, of patients with seemingly sporadic PD in these two populations [4,9,11].…”

mentioning

confidence: 99%

“…Remarkably, it accounts for 29% of Ashkenazi Jews and 37% of North African Arabs with familial parkinsonism and for 13 and 30%, respectively, of patients with seemingly sporadic PD in these two populations [4,9,11]. Furthermore, the Lrrk2 G2385R and R1628P substitutions are risk factors for sporadic PD in Asian populations [12][13][14].…”

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confidence: 99%

Update on the Functional Biology of Lrrk2

Melrose

2008

Future Neurol.

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The etiology of Parkinson's disease (PD) was long thought to be due to environmental factors. Following the discovery of autosomal-dominant mutations in the α-synuclein gene, and later recessive mutations in the DJ-1, Parkin and PINK-1 genes, the field of PD genetics exploded. In 2004, it was discovered that mutations in the PARK8 locus -leucine-rich repeat kinase 2 (LRRK2, Lrrk2) -are the most important genetic cause of autosomal-dominant PD. Lrrk2 substitutions also account for sporadic PD in certain ethnic populations and have been shown to increase the risk of PD in Asian populations. Drug therapies targeting Lrrk2 activity may therefore be beneficial to both familial and sporadic PD patients, hence understanding the role of Lrrk2 in health and disease is critical. This review aims to highlight the research effort concentrated on elucidating the functional biological role of Lrrk2, and to provide some future therapeutic perspectives.

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LRRK2G2019S as a Cause of Parkinson's Disease in Ashkenazi Jews

Cited by 642 publications

References 8 publications

Epidemiology and etiology of Parkinson’s disease: a review of the evidence

Epidemiology and etiology of Parkinson’s disease: a review of the evidence

Parkinson's Disease Therapeutics: New Developments and Challenges Since the Introduction of Levodopa

Update on the Functional Biology of Lrrk2

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