| Summary: | <p>Abstract</p> <p>Background</p> <p>Parkinson's disease (PD) is the most prevalent incurable neurodegenerative movement disorder. Mutations in <it>LRRK2 </it>are associated with both autosomal dominant familial and sporadic forms of PD. <it>LRRK2 </it>encodes a large putative serine/threonine kinase with GTPase activity. Increased LRRK2 kinase activity plays a critical role in pathogenic LRRK2 mutant-induced neurodegeneration <it>in vitro</it>. Little is known about the physiological function of LRRK2.</p> <p>Results</p> <p>We have recently identified a <it>Drosophila </it>line with a P-element insertion in an ortholog gene of human <it>LRRK2 </it>(<it>dLRRK</it>). The insertion results in a truncated <it>Drosophila </it>LRRK variant with N-terminal 1290 amino acids but lacking C-terminal kinase domain. The homozygous mutant fly develops normally with normal life span as well as unchanged number and pattern of dopaminergic neurons. However, <it>dLRRK </it>mutant flies were selectively sensitive to hydrogen peroxide induced stress but not to paraquat, rotenone and β-mercaptoethanol induced stresses.</p> <p>Conclusion</p> <p>Our results indicate that inactivation of <it>d</it>LRRK kinase activity is not essential for fly development and suggest that inhibition of LRRK activity may serve as a potential treatment of PD. However, <it>d</it>LRRK kinase activity likely plays a role in protecting against oxidative stress.</p>
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