The relationship between parkin and protein aggregation in neurodegenerative diseases

Preeti Khandelwal

doi:10.3389/fpsyt.2010.00015

Abstract

The most prominent changes in neurodegenerative diseases are protein accumulation and inclusion formation. Several neurodegenerative diseases, including Alzheimer's, the Synucleinopathies and Tauopathies share several overlapping clinical symptoms manifest in Parkinsonism, cognitive decline and dementia. As degeneration progresses in the disease process, clinical symptoms suggest convergent pathological pathways. Biochemically, protein cleavage, ubiquitination and phosphorylation seem to play fundamental roles in protein aggregation, inclusion formation and inflammatory responses. In the following we provide a synopsis of the current knowledge about protein accumulation and astrogliosis as a common denominator in neurodegenerative diseases, and we propose insights into protein degradation and anti-inflammation. We review the E3-ubiquitin ligase and other possible functions of parkin as a suppressant of inflammatory signs and a strategy to clear amyloid proteins in neurodegenerative diseases.

Highlights

Parkin as an E3-ubiquitin ligase Parkin is an E3 ubiquitin-protein ligase, which facilitates proteasomal degradation of misfolded proteins (Shimura et al, 2000)
Parkin fusion proteins interact with the synaptic vesicle protein, CDC-rel-1
The ability of parkin to function as an E3 ubiquitin-protein ligase and its relationship with proteasomal function suggest that parkin may contribute to proteasomal clearance of α-Synuclein and Aβ, attenuating the toxicity of these amyloids

Summary

Introduction

Parkin as an E3-ubiquitin ligase Parkin is an E3 ubiquitin-protein ligase, which facilitates proteasomal degradation of misfolded proteins (Shimura et al, 2000). Parkin may reduce the levels of intracellular proteins by ubiquitination and proteasomal degradation in cell culture and animal models.

Results

Conclusion