Format

Send to

Choose Destination
See comment in PubMed Commons below
Biochemistry. 2007 Jun 26;46(25):7325-36. Epub 2007 Jun 2.

Nitration in neurodegeneration: deciphering the "Hows" "nYs".

Author information

  • 1Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA. m-reynolds@md.northwestern.edu

Abstract

Recent literature has ushered in a new awareness of the diverse post-translational events that can influence protein folding and function. Among these modifications, protein nitration is thought to play a critical role in the onset and progression of several neurodegenerative diseases. While previously considered a late-stage epiphenomenon, nitration of protein tyrosine residues appears to be an early event in the lesions of amyotrophic lateral sclerosis, Parkinson's disease, and Alzheimer's disease. The advent of highly specific biochemical and immunological detection methods reveals that nitration occurs in vivo with biological selectively and site specificity. In fact, nitration of only a single Tyr residue is often sufficient to induce profound changes in the activity of catalytic proteins and the three-dimensional conformation of structural proteins. Presumably, nitration modifies protein function by altering the hydrophobicity, hydrogen bonding, and electrostatic properties within the targeted protein. Most importantly, however, nitrative injury may represent a unifying mechanism that explains how genetic and environmental causes of neurological disease manifest a singular phenotype. In this review and synthesis, we first examine the pathways of protein nitration in biological systems and the factors that influence site-directed nitration. Subsequently, we turn our attention to the structural implications of site-specific nitration and how it affects the function of several neurodegeneration-related proteins. These proteins include Mn superoxide dismutase and neurofilament light subunit in amyotrophic lateral sclerosis, alpha-synuclein and tyrosine hydroxylase in Parkinson's disease, and tau in Alzheimer's disease.

[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for American Chemical Society
    Loading ...
    Write to the Help Desk