LRRK2 structure and function

As opposed to a-syn, LRRK2 had not been cloned or thoroughly annotated when missense mutations were identified in PD cases. Bioinformatic prediction strongly suggested that LRRK2 encodes a GTPase-like domain together with a kinase domain, thereby placing LRRK2 within the fraction of the proteome considered modifiable with small molecules or intervention therapies. The potential for LRRK2 as a therapeutic target depends not only on activities of the protein associated with PD, but on normal function and the relation between health and disease. For example, generalized inhibition of LRRK2 activity may not be compatible with normal cellular function, or inhibition of one particular aspect of LRRK2 activity may not influence another activity that underlies
disease mechanisms. Deep insight into LRRK2-related biology will provide the background necessary for rationally designed therapeutic approaches.