Parkinson's disease and immune system: is the culprit LRRKing in the periphery?

Abstract

Leucine-rich repeat kinase 2 (LRRK2) is a large multidomain kinase/GTPase that has been recently linked to three pathological conditions: Parkinson's disease; Crohn's disease; and leprosy. Although LRRK2 physiological function is poorly understood, a potential role in inflammatory response is suggested by its high expression in immune cells and tissues, its up-regulation by interferon γ, and its function as negative regulator of the immune response transcription factor NFAT1. In this review we discuss the most recent findings regarding how LRRK2 could be a player in the inflammatory response and we propose a scenario where the detrimental effects mediated by Parkinson's disease LRRK2 mutations may initiate in the periphery and extend to the central nervous system as a consequence of increased levels of pro-inflammatory factors permeable to the blood brain barrier.

• Authors: Elisa Greggio, Laura Civiero, Marco Bisaglia, Luigi Bubacco
• Journal: Journal of neuroinflammation (J Neuroinflammation) Vol. 9 Pg. 94 (Jul 09 2012) ISSN: 1742-2094 [Electronic] England
• PMID: 22594666 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Inflammation Mediators
• LRRK2 protein, human
• Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
• Protein Serine-Threonine Kinases

Topics

• Animals
• Blood-Brain Barrier (immunology, metabolism)
• Humans
• Inflammation Mediators (metabolism, physiology)
• Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
• Parkinson Disease (enzymology, genetics, immunology)
• Peripheral Nervous System (enzymology, immunology)
• Protein Serine-Threonine Kinases (genetics, metabolism, physiology)
• Up-Regulation (genetics, immunology)