[Frontiers in Bioscience, Landmark, 20, 263-279, January 1, 2015]

Lipid rafts involvement in the pathogenesis of parkinson’s disease

Shin-ichiro Kubo 1 , Taku Hatanos 1 , Nobutaka Hattori 1

1Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan


1. Abstract
2. Introduction
3. Lipid rafts
    3.1. Lipid raft concept
    3.2. Lipid rafts becoming a reality
    3.3. Biological roles of lipid rafts
4. Parkinson’s disease and lipid rafts
    4.1. Parkinson’s disease
      4.1.1 Monogenic forms of PD
    4.2. Lipid rafts in PD
      4.2.1. α-Synuclein
      4.2.2 LRRK2
      4.2.3 Parkin
      4.2.4. DJ-1
      4.2.5. Idiopathic PD
5. Summary and perspective
6. Acknowledgment
7. References


Parkinson’s disease (PD) is one of the most common neurodegenerative diseases affecting an increasing number of people worldwide with the aging society. Although the etiology of PD remains largely unknown, it is now clear that genetic factors contribute to the pathogenesis of the disease. Recently, several causative genes have been identified in mendelian forms of PD. Growing evidence indicates that their gene products play important roles in oxidative stress response, mitochondrial function, and the ubiquitin-proteasome system, which are also implicated in idiopathic PD, suggesting that these gene products share a common pathway to nigral degeneration in both familial and idiopathic PD. Interestingly, several lines of evidence show that the gene products associate with lipid rafts which are thought to be involved in important cellular functions such as membrane trafficking, signal transduction, and cytoskeletal organization. Lipid rafts are cholesterol- and sphingolipid-enriched microdomains on the cell membranes that provide a highly saturated and viscous physicochemical microenvironment to promote protein–lipid and protein–protein interactions. In this article, we will review studies focusing on PD in association with lipid rafts and discuss implication of lipid rafts in the pathogenesis of PD.


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Key Words: Lipid Rafts, Parkinson’s disease, Alpha-Synuclein, LRRK2, Parkin, Review

Send correspondence to: Shin-ichiro Kubo, Department of Neurology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo, Tokyo 113-8421, Japan, Tel: 81-3-5684-0476, Fax: 81-3-3813-7440, E-mail: skubo@juntendo.ac.jp