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Eukaryon

Class Year

2008

Keywords

substantia nigra dopaminergic neurons, Lewy Bodies, α-synuclein phosphorylation, Tyrosine phosphorylation, α-synuclein nitration, synphilin

Abstract

Parkinson’s disease (PD) is the second most common neurodegenerative disease, affecting six million people worldwide. PD results from the specific loss of substantia nigra dopaminergic neurons. Aggregation of one protein, α-synuclein, is characteristic of PD. This aggregation is thought to be a critical step in the etiology of the disease. While the molecular mechanism of α-synuclein aggregation remains unknown, nitrative stress and phosphorylation have been implicated in α-synuclein modification and aggregation. In fact, nitration of α-synuclein tyrosine residues 39, 125, 133 or 136, may be an early event in aggregates, Lewy bodies, seen in PD. Furthermore, nitrative stress leads to the induction of α-synuclein aggregation at a higher rate than seen in other PD mutants. This aggregation may result from a stabilization of pre-assembled α-synuclein filaments, which, upon nitration, may withstand denaturing conditions and enhance formation of SDS-insoluble, heat-stable high mass aggregates. Phosphorylation of a-synuclein also appears to play a critical role in the formation of aggregates. Extensive studies indicate that α-synuclein found in PD patient brains is extensively phosphorylated. Phosphorylation of ser-129 may enhance formation of aggregates reminiscent of Lewy bodies in vitro and in vivo. Nitration and phosphorylation of α-synuclein may be key to the mechanisms underlying the formation of Lewy bodies in PD.

Disclaimer

Eukaryon is published by students at Lake Forest College, who are solely responsible for its content. The views expressed in Eukaryon do not necessarily reflect those of the College. Articles published within Eukaryon should not be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.

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