Abstract
PD (Parkinson's disease) is a common neurodegenerative disease clinically characterized by bradykinesia, rigidity and resting tremor. Recent studies have proposed that synaptic dysfunction, implicated in numerous studies of animal models of PD, might be a key factor in PD. The molecular defects that lead to PD progression might be hidden at the presynaptic neuron: in fact accumulating evidence has shown that the majority of the genes linked to PD play a critical role at the presynaptic site. In the present paper, we focus on the presynaptic function of LRRK2 (leucine-rich repeat kinase 2), a protein that mutated represents the main genetic cause of familial PD described to date. Neurotransmission relies on proper presynaptic vesicle trafficking; defects in this process, variation in dopamine flow and alteration of presynaptic plasticity have been reported in several animal models of LRRK2 mutations. Furthermore, impaired dopamine turnover has been described in presymptomatic LRRK2 PD patients. Thus, given the pathological events occurring at the synapses of PD patients, the presynaptic site may represent a promising target for early diagnostic therapeutic intervention.
- dopamine
- leucine-rich repeat kinase 2 (LRRK2)
- Parkinson's disease
- presynaptic dysfunction
- synaptic vesicle
Footnotes
LRRK2: Function and Dysfunction: A Biochemical Society Focused Meeting held at Royal Holloway, University of London, Egham, UK, 28–30 March 2012. Organized and Edited by Patrick Lewis (University College London, U.K.) and Dario Alessi (Dundee, U.K.).
Abbreviations: AP-2, adaptor protein 2; BAC, bacterial artificial chromosome; COR, C-terminal of Ras of complex proteins; KO, knockout; LC3, light chain 3; LRRK2, leucine-rich repeat kinase 2; MKK, mitogen-activated protein kinase kinase; NSF, N-ethylmaleimide-sensitive factor; PD, Parkinson's disease; PINK1, phosphatase and tensin homologue deleted on chromosome 10-induced putative kinase 1; ROC, Ras of complex proteins; SNARE, soluble NSF-attachment protein receptor; SNpc, substantia nigra pars compacta; SV, synaptic vesicle; SV2A, synaptic vesicle protein 2A
- © The Authors Journal compilation © 2012 Biochemical Society