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Assaying the Kinase Activity of LRRK2 in vitro
Published on: January 18, 2012
Insights into LRRK2 function and dysfunction from transgenic and knockout rodent models.
Maximilian Sloan1, Javier Alegre-Abarrategui, Richard Wade-Martins
1Oxford Parkinson's Disease Centre, Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, U.K.
Biochemical Society Transactions
|September 20, 2012
Summary
Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are linked to Parkinson's disease (PD). LRRK2 rodent models, though imperfect, offer insights into LRRK2's role in PD pathogenesis and potential therapies.
Area of Science:
- Neuroscience
- Genetics
- Molecular Biology
Background:
- Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are a known cause of autosomal dominant Parkinson's disease (PD).
- LRRK2-linked PD is clinically indistinguishable from sporadic PD, highlighting the need for effective disease models.
- Understanding LRRK2's function is crucial for developing targeted therapies for Parkinson's disease.
Purpose of the Study:
- To review findings from LRRK2 rodent models in Parkinson's disease research.
- To elucidate the normal and pathological functions of LRRK2.
- To connect altered cellular processes and identify mechanisms of LRRK2 dysfunction for therapeutic development.
Main Methods:
- Review of studies utilizing transgenic LRRK2 expression in rodents.
- Analysis of data from Lrrk2 knockout rodent models.
- Synthesis of findings to identify common pathways affected by LRRK2.
Main Results:
- LRRK2 rodent models partially recapitulate PD pathology.
- LRRK2 is implicated in cytoskeletal dynamics, synaptic function, dopamine homeostasis, and autophagy.
- Disparate cellular processes altered by LRRK2 dysfunction are being identified.
Conclusions:
- LRRK2 rodent models are valuable tools for studying Parkinson's disease.
- Further research is needed to fully understand the contribution of LRRK2 pathways to PD.
- Insights from these models may lead to novel therapeutic strategies for Parkinson's disease.
