Although the physiological function of LRRK2 protein remains largely elusive, increasing evidence suggests that it plays a role in innate immunity, a process that also has been implicated in neurodegenerative diseases, including PD.
Collectively, these results suggest that LRRK2 could be a potential molecular target for developing therapeutics to treat Mn-related neurodegenerative disorders.
Four of these validated variants were nonsense mutations, six were observed in genes directly or indirectly related to neurodegenerative disorders (NDs), such as LPA, LRRK2, and FGF20.
Implications regarding an autosomal dominant neurodegenerative disorder (PARK 8) in which four different neuropathological diagnoses were found at autopsy are discussed.
In summary, the effective shRNA against LRRK2 R1441 alleles described herein suggests that RNAi-based therapy of inherited Parkinson's disease is a viable approach towards developing effective therapeutic interventions for this serious neurodegenerative disease.
Interestingly, Rab10 is a key substrate of leucine-rich repeat kinase 2 (LRRK2), a serine/threonine protein kinase genetically associated with the second most common neurodegenerative disease Parkinson's disease.
Mutations in LRRK2 (leucine-rich repeat kinase 2) are the most frequent genetic lesions so far found in familial as well as sporadic forms of PD (Parkinson's disease), a neurodegenerative disease characterized by the dysfunction and degeneration of dopaminergic and other neuronal types.
Our results revealed clinical heterogeneity of the LRRK2p.I2012T substitution, and demonstrated the use of targeted NGS for genetic diagnosis in multiplex families with PD or mixed neurodegenerative disorders.
Parkinson disease is a progressive neurodegenerative disease for which leucine-rich repeat kinase 2 (LRRK2 carriers) p.G2019S confers substantial genotypic and population attributable risk.
Pathogenic Lrrk2Y1699C substitution observed in a large German-Canadian kindred presents a neurodegenerative disorder that is reminiscent of amyotrophic lateral sclerosis and Parkinsonism-Dementia Complex.
Several mutations in leucine rich repeat kinase 2 (LRRK2) gene have been associated with pathogenesis of Parkinson's disease (PD), a neurodegenerative disorder marked by resting tremors, and rigidity, leading to Postural instability.
Since LRRK2 is detected in tau-positive inclusions in brain tissue affected by various neurodegenerative disorders, including PD, LRRK2-stimulated phosphorylation of tau by GSK-3β may be involved in development of pathological features in the initial stage of PD.
The aim of this study was to identify new potentially active compounds for three protein targets, tropomyosin receptor kinase A (TrkA), <i>N</i>-methyl-d-aspartate (NMDA) receptor, and leucine-rich repeat kinase 2 (LRRK2), that are related to various neurodegenerative diseases such as Alzheimer's, Parkinson's, and neuropathic pain.