Parkinson’s disease (PD) is the second most common progressive neurodegenerative disorder affecting more than 1% of the population over 65 years of age. Dominant mutations in the leucine-rich repeat kinase 2 (lrrk2) gene are found associated with both familial and sporadic cases and represent the most frequent genetic lesions associated with PD. Remarkably, lrrk2 mutations cause PD with age-rel...

BACKGROUND Idiopathic Parkinson's disease (IPD) and LRRK2-associated PD (LRRK2-PD) might be expected to differ clinically since the neuropathological substrate of LRRK2-PD is heterogeneous. The range and severity of extra-nigral nonmotor features associated with LRRK2 mutations is also not well-defined. OBJECTIVE To evaluate the prevalence and time of onset of nonmotor symptoms (NMS) in LRRK2...

Mutations in LRRK2 underlie an autosomal-dominant, inherited form of Parkinson's disease (PD) that mimics the clinical features of the common "sporadic" form of PD. The LRRK2 protein includes putative GTPase, protein kinase, WD40 repeat, and leucine-rich repeat (LRR) domains of unknown function. Here we show that PD-associated LRRK2 mutations display disinhibited kinase activity and induce a pr...

LRRK2 (leucine-rich repeat protein kinase 2) is mutated in a significant number of Parkinson's disease patients, but still little is understood about how it is regulated or functions. In the present study we have demonstrated that 14-3-3 protein isoforms interact with LRRK2. Consistent with this, endogenous LRRK2 isolated from Swiss 3T3 cells or various mouse tissues is associated with endogeno...

Leucine-rich repeat kinase 1 and 2 (LRRK1 and LRRK2) are large multidomain proteins containing kinase, GTPase and multiple protein-protein interaction domains, but only mutations in LRRK2 are linked to familial Parkinson's disease (PD). Independent studies suggest that LRRK2 exists in the cell as a complex compatible with the size of a dimer. However, whether this complex is truly a homodimer o...

PD (Parkinson's disease) is the most common neurodegenerative movement disorder. Mutations in LRRK2 (leucine-rich repeat kinase 2) gene are linked to the most common inherited and sporadic PD. Overexpression of LRRK2 and its mutants could induce mitochondrial-dependent neuronal apoptosis. However, the underlying mechanism remains elusive. We have identified several novel LRRK2 interacting prote...

Missense mutations in the Leucine-Rich Repeat protein Kinase 2 (LRRK2) gene are the most common genetic predisposition to develop Parkinson's disease (PD) (Farrer et al., 2005; Skipper et al., 2005; Di Fonzo et al., 2006; Healy et al., 2008; Paisan-Ruiz et al., 2008; Lesage et al., 2010). LRRK2 is a large multi-domain phosphoprotein with a GTPase domain and a serine/threonine protein kinase dom...

The enhanced neurotoxicity of the Parkinson's disease-associated LRRK2 mutant, G2019S, than its wild-type counter-part has recently been reported. Overexpression of LRRK2 (G2019S) in cultured neural cells results in caspase-3-dependent apoptosis via a yet undefined signaling pathway. Elucidation of the mechanism underlying LRRK2 (G2019S) neurotoxicity may offer new insights into the pathogenesi...

OBJECTIVE Olfactory impairment is a potential marker for impending phenoconversion to Parkinson disease (PD) that may precede the development of disease by several years. Because of low specificity, it may be of greater predictive value in those with genetic mutations and its potential as a marker for developing LRRK2 PD should be evaluated. METHODS We examined olfactory identification in 126...

Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most frequent cause of genetic Parkinson's disease (PD). The biological function of LRRK2 and how mutations lead to disease remain poorly defined. It has been proposed that LRRK2 could function in gene transcription regulation; however, this issue remains controversial. Here, we investigated in parallel gene and microRNA (miRNA) transcri...