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Review
. 2018;16(9):1348-1357.
doi: 10.2174/1570159X16666180222165418.

The Role of LRRK2 in Neurodegeneration of Parkinson Disease

Qin Rui  1 , Haibo Ni  2 , Di Li  3 , Rong Gao  2 , Gang Chen  4
Affiliations
Review

The Role of LRRK2 in Neurodegeneration of Parkinson Disease

Qin Rui et al. Curr Neuropharmacol. 2018.

Abstract

The leucine-rich repeat kinase 2 (LRRK2) gene and α-synuclein gene (SNCA) are the key influencing factors of Parkinson's disease (PD). It is reported that dysfunction of LRRK2 may influence the accumulation of α-synuclein and its pathology to alter cellular functions and signaling pathways by the kinase activation of LRRK2. The accumulation of α-synuclein is one of the main stimulants of microglial activation. Microglia are macrophages that reside in the brain, and activation of microglia is believed to contribute to neuroinflammation and neuronal death in PD. Therefore, clarifying the complex relationship among LRRK2, α-synuclein and microglials could offer targeted clinical therapies for PD. Here, we provide an updated review focused on the discussion of the evidence supporting some of the key mechanisms that are important for LRRK2-dependent neurodegeneration in PD.

Keywords: Leucine-rich repeat kinase 2; MAPK; Parkinson`s disease; microglia; neurodegeneration; neuroinflammation.; α-synuclein.

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Figures

Fig. (1)
Fig. (1)
LRRK2 domain struture and its possible mechanisms of neurodegeneration in PD. GTPase: guanosine triphosphatase; LRRK2: leucine-rich repeat kinase; ERK: extracellular signal-regulated kinase; MAPKKs: mitogen-activated protein kinase kinases; JNK: c-Jun N-terminal kinase; NF-κB: nuclear factor kappa-B; TLR2/4: Toll-like receptor 2/4; MK2/3: MAPKAPK2/3; SNpc: substantia nigra pars compacta; PD: Parkinson disease.
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