Accumulation of misfolded protein through nitrosative stress linked to neurodegenerative disorders

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Protein quality control is a critical feature of intracellular homeostasis. In particular, unfolded or misfolded proteins resulting from environmental stresses or free radicals are rapidly degraded via the ubiquitin-proteasome pathway. Nitric oxide (NO), a free radical gas, has been reported to be involved in such processes as vasorelaxation and neurotransmission. Conversely, NO also is implicated in neuronal cell death or neurodegeneration. Recent reports suggest that S-nitrosylation of proteins is a significant cause of neural dysfunction leading to neurodegenerative disorders. Specifically, S-nitrosylation of parkin eventually leads to the accumulation of unfolded proteins and subsequent neuronal death. The focus of this review is the identity of the target of NO. Nitrosative stress prevents normal functioning of the endoplasmic reticulum (ER) via S-nitrosylation of protein-disulfide isomerase (PDI), which is located in the ER lumen. This may contribute to the accumulation of misfolded proteins, as well as sustained activation of the unfolded protein response (UPR) pathway. These phenomena may be linked to the development of sporadic neurodegenerative diseases.

Original languageEnglish
Pages (from-to)597-601
Number of pages5
JournalAntioxidants and Redox Signaling
Volume9
Issue number5
DOIs
Publication statusPublished - May 2007
Externally publishedYes

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Neurodegenerative Diseases
Nitric Oxide
Endoplasmic Reticulum
Free Radicals
Protein Disulfide-Isomerases
Unfolded Protein Response
Protein Unfolding
Proteins
Protein S
Proteasome Endopeptidase Complex
Ubiquitin
Vasodilation
Synaptic Transmission
Quality Control
Neurodegenerative diseases
Homeostasis
Cell Death
Gases
Cell death
Quality control

ASJC Scopus subject areas

  • Biochemistry

Cite this

Accumulation of misfolded protein through nitrosative stress linked to neurodegenerative disorders. / Uehara, Takashi.

In: Antioxidants and Redox Signaling, Vol. 9, No. 5, 05.2007, p. 597-601.

Research output: Contribution to journalArticle

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