Molecular basis of Parkinson's disease linked with mutations in the LRRK2 gene

• Published in: Molekuliarnaia biologiia Vol. 48; no. 1; p. 3
• Main Authors: Pchelina, S N, emel'ianov, A K, Usenko, T S
• Format: Journal Article
• Language: Russian
• Published: Russia (Federation) 01.01.2014
• Subjects: Amino Acid Substitution; Animals; Apoptosis - genetics; Cytoskeleton - genetics; Cytoskeleton - metabolism; Cytoskeleton - pathology; Dopaminergic Neurons - metabolism; Dopaminergic Neurons - pathology; Humans; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; Mutation, Missense; Parkinson Disease - genetics; Parkinson Disease - metabolism; Parkinson Disease - pathology; Pars Compacta - metabolism; Pars Compacta - pathology; Protein Aggregation, Pathological - genetics; Protein Aggregation, Pathological - metabolism; Protein Aggregation, Pathological - pathology; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Signal Transduction - genetics
• ISSN: 0026-8984

Parkinson's disease (PD) is a common neurodegenerative disorder. Disease symptoms correlate with the degeneration of dopaminergic neurons in substantia nigra pars compacta. A number of factors are supposed to take part in PD pathogenesis including alpha-synuclein aggregation, oxidative stress, mitochondrial dysfunction and apoptosis, although the precise molecular mechanism of neudegeneration remains unknown. PD is generally a sporadic neuro- logical disorder, however, rare monogenic forms have been described during previous 15 years. Despite of the fact that mutations in the leucine-rich repeat kinase (LRRK2) gene are the most common cause of inherited forms of PD known today, the mechanisms by which mutations in the LRRK2 gene lead to disease remain unclear. It's difficult to understand the signaling pathways, regulated by LRRK2 in the absence of its clear physiological substrates. The G2019S substitution was shown to be the most common in mutations' spectrum of the LRRK2 gene in different populations which makes it easier to reveal patients with LRRK2-associated PD. In this review LRRK2 influence on protein aggregation, cytoskeletal dynamics, apoptosis rate and inflammatory response is discussed. Groups of patients with inherited forms of PD with known etiology are worth to be included into investigations. It could promote our un- derstanding of the mechanisms of neurodegeneration in more common sporadic cases.