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Apoptotic mechanisms in mutant LRRK2-mediated cell death

Iaccarino, Ciro and Crosio, Claudia and Vitale, Carmine and Sanna, Giovanna and Carrì, Maria Teresa and Barone, Paolo (2007) Apoptotic mechanisms in mutant LRRK2-mediated cell death. Human Molecular Genetics, Vol. 16 (11), p. 1319-1326. eISSN 1460-2083. Article.

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DOI: 10.1093/hmg/ddm080

Abstract

Mutations in the gene coding for leucine-rich repeat kinase 2 (LRRK2) cause autosomal-dominant Parkinson's disease. The pathological mutations have been associated with an increase of LRRK2 kinase activity, although its physiological substrates have not been identified yet. The data we report here demonstrate that disease-associated mutant LRRK2 cell toxicity is due to mitochondria-dependent apoptosis. Transient transfection of mutant LRRK2 leads to neuronal death with clear apoptotic signs. Soluble caspase inhibitors or the genetic ablation of Apaf1 protects cells from apoptotic death. Moreover, we explored the function of two protein domains in LRRK2 (LRR and WD40) and demonstrate that the lack of these protein domains has a protective effect on mitochondria dysfunctions induced by mutant LRRK2.

Item Type:Article
ID Code:269
Status:Published
Refereed:Yes
Uncontrolled Keywords:Parkinson's disease, pathological mutations, cell toxicity, mitochondria-dependent apoptosis
Subjects:Area 05 - Scienze biologiche > BIO/11 Biologia molecolare
Divisions:001 Università di Sassari > 01 Dipartimenti > Scienze fisiologiche, biochimiche e cellulari
Publisher:Oxford University Press
eISSN:1460-2083
Additional Information:Pubblicato online il 4 aprile 2007.
Deposited On:18 Aug 2009 10:01

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