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Interaction of LRRK2 and α-Synuclein in Parkinson’s Disease

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Leucine-Rich Repeat Kinase 2 (LRRK2)

Part of the book series: Advances in Neurobiology ((NEUROBIOL,volume 14))

Abstract

Parkinson’s disease (PD) is a progressively debilitating neurodegenerative syndrome. It is best described as a movement disorder characterized by motor dysfunctions, progressive degeneration of dopaminergic neurons of the substantia nigra pars compacta, and abnormal intraneuronal protein aggregates, named Lewy bodies and Lewy neurites. Nevertheless, knowledge of the molecular events leading to this pathophysiology is incomplete. To date, only mutations in the α-synuclein and LRRK2-encoding genes have been associated with typical findings of clinical and pathologic PD. LRRK2 appears to have a central role in the pathogenesis of PD as it is associated with α-synuclein pathology and other proteins implicated in neurodegeneration. Thus, LRRK2 dysfunction may influence the accumulation of α-synuclein and its pathology through diverse pathomechanisms altering cellular functions and signaling pathways, including immune system, autophagy, vesicle trafficking, and retromer complex modulation. Consequently, development of novel LRRK2 inhibitors can be justified to treat the neurodegeneration associated with abnormal α-synuclein accumulation.

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Acknowledgments

I thank Dr. Andrew West for a critical review of this manuscript.

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The author declares no conflicts of interest.

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Authors and Affiliations

  1. Faculty of Medicine, School of Medical Sciences, University of New South Wales, Sydney, NSW, 2052, Australia

    João Paulo Lima Daher

  2. Neuroscience Research Australia, Barker St, Randwick, NSW, 2031, Australia

    João Paulo Lima Daher

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  1. Biomedical Research Foundation of the Academy of Athens (BRFAA), Athens, Greece

    Hardy J. Rideout

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Daher, J.P.L. (2017). Interaction of LRRK2 and α-Synuclein in Parkinson’s Disease. In: Rideout, H. (eds) Leucine-Rich Repeat Kinase 2 (LRRK2). Advances in Neurobiology, vol 14. Springer, Cham. https://doi.org/10.1007/978-3-319-49969-7_11

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