Nitrosative Stress in the ER: A New Role for S-Nitrosylation in Neurodegenerative Diseases

• Published in: ACS chemical biology Vol. 1; no. 6; pp. 355 - 358
• Main Authors: Forrester, Michael T, Benhar, Moran, Stamler, Jonathan S
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 21.07.2006
• Subjects: Animals; Endoplasmic Reticulum - chemistry; Endoplasmic Reticulum - metabolism; Humans; Neurodegenerative Diseases - metabolism; Nitric Oxide - chemistry; Nitric Oxide - physiology; Nitrosation; Protein Folding
• ISSN: 1554-8929; 1554-8937
• DOI: 10.1021/cb600244c

S-Nitrosylation, the covalent addition of a nitrogen monoxide group to a cysteine thiol, has been shown to modify the function of a broad spectrum of mammalian, plant, and microbial proteins and thereby to convey the ubiquitous influence of nitric oxide on cellular signal transduction and host defense. Accumulating evidence indicates that dysregulated, diminished, or excessive S-nitrosylation may be implicated in a wide range of pathophysiological conditions. A recent study establishes a functional relationship between inhibitory S-nitrosylation of the redox enzyme protein disulfide isomerase (PDI), defects in regulation of protein folding within the endoplasmic reticulum (ER), and neurodegeneration. Further, an examination of human brains afflicted with Parkinson’s or Alzheimer’s disease supports a causal role for the S-nitrosylation of PDI and consequent ER stress in these prevalent neurodegenerative disorders.