LRRK2 and Autophagy

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

Abstract

Leucine-rich repeat kinase 2 (LRRK2) has been implicated in a wide range of cellular processes, including the catabolic pathways collectively described as autophagy. In this chapter, the evidence linking LRRK2 to autophagy will be examined, along with how regulation of autophagy and lysosomal pathways may provide a nexus between the physiological function of this protein and the different diseases with which it has been associated. Data from cellular and animal models for LRRK2 function and dysfunction support a role in the regulation and control of autophagic pathways in the cell, although the extant results do not provide a clear indication as to whether LRRK2 is a positive or negative regulator of these pathways, and there are conflicting data as to the impact of mutations in LRRK2 causative for Parkinson’s disease. Given that LRRK2 is a priority drug target for Parkinson’s, the evidence suggesting that knockout or inhibition of LRRK2 can result in deregulation of autophagy may have important implications and is discussed in the context of our wider understanding of LRRK2.

Keywords

LRRK2 Macroautophagy Catabolism Parkinson’s disease Lysosomes Autophagosomes 

Notes

Acknowledgments

The authors wish to acknowledge generous funding from the Medical Research Council (grants MR/L010933/1 and MR/N026004/1), Parkinson’s UK (Fellowship F1002), the Rosetrees Trust, and the Michael J. Fox Foundation.

Conflict of Interest

The author declares no conflicts of interest.

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© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.School of PharmacyUniversity of ReadingReadingUK
  2. 2.Department of Molecular NeuroscienceUCL Institute of NeurologyLondonUK

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