LRRK2 in peripheral and central nervous system innate immunity: its link to Parkinson's disease

Biochem Soc Trans. 2017 Feb 8;45(1):131-139. doi: 10.1042/BST20160262.

Abstract

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are found in familial and idiopathic cases of Parkinson's disease (PD), but are also associated with immune-related disorders, notably Crohn's disease and leprosy. Although the physiological function of LRRK2 protein remains largely elusive, increasing evidence suggests that it plays a role in innate immunity, a process that also has been implicated in neurodegenerative diseases, including PD. Innate immunity involves macrophages and microglia, in which endogenous LRRK2 expression is precisely regulated and expression is strongly up-regulated upon cell activation. This brief report discusses the current understanding of the involvement of LRRK2 in innate immunity particularly in relation to PD, critically examining its role in myeloid cells, particularly macrophages and microglia.

Keywords: Parkinson's disease; induced pluripotent stem cells; leucine-rich repeat kinase; macrophages; microglia; neuroinflammation.

Publication types

  • Review

MeSH terms

  • Central Nervous System / enzymology
  • Central Nervous System / immunology*
  • Humans
  • Immunity, Innate / immunology*
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / genetics
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / immunology*
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / metabolism
  • Macrophages / immunology
  • Microglia / immunology
  • Models, Immunological
  • Mutation / immunology
  • Parkinson Disease / enzymology
  • Parkinson Disease / genetics
  • Parkinson Disease / immunology*
  • Peripheral Nervous System / enzymology
  • Peripheral Nervous System / immunology*

Substances

  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2