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Biochem Soc Trans. 2012 Oct;40(5):1111-6.

Presynaptic dysfunction in Parkinson's disease: a focus on LRRK2.

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Department of Biology, University of Padova, Via Ugo Bassi 58/B, Padua, Italy.


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.

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