Heterodimerization of Lrrk1-Lrrk2: Implications for LRRK2-associated Parkinson disease

Justus C. Dachsel, Kenya Nishioka, Carles Vilariño-Güell, Sarah J. Lincoln, Alexandra I. Soto-Ortolaza, Jennifer Kachergus, Kelly M. Hinkle, Michael G. Heckman, Barbara Jasinska-Myga, Julie P. Taylor, Dennis W. Dickson, Rachel A. Gibson, Faycal Hentati, Owen A. Ross, Matthew J. Farrer

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


LRRK2 mutations are recognized as the most frequent genetic cause of both familial and sporadic parkinsonism identified to date. A remarkable feature of this form of parkinsonism is the variable penetrance of symptom manifestation resulting in a wide range of age-at-onset in patients. Herein we use a functional approach to identify the Lrrk1 protein as a potential disease modifier demonstrating an interaction and heterodimer formation with Lrrk2. In addition, evaluation of LRRK1 variants in our large Lrrk2 p.G2019S-parkinsonism series from a Tunisian (n=145) identified a missense mutation (p.L416M) resulting in an average 6.2 years younger age at disease onset. In conclusion we show that the interaction of Lrrk1-Lrrk2 can form protein dimers and this interaction may influence the age of symptomatic manifestation in Lrrk2-parkinsonism patients.

Original languageEnglish (US)
Pages (from-to)210-214
Number of pages5
JournalMechanisms of Ageing and Development
Issue number3
StatePublished - Mar 2010


  • Dimerization
  • Genetics
  • LRRK2
  • P.G2019S
  • PD

ASJC Scopus subject areas

  • Aging
  • Developmental Biology


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