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 language | English |
|---|---|
| Pages (from-to) | 597-601 |
| Number of pages | 5 |
| Journal | Antioxidants and Redox Signaling |
| Volume | 9 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - May 2007 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Accumulation of misfolded protein through nitrosative stress linked to neurodegenerative disorders
AU - Uehara, Takashi
PY - 2007/5
Y1 - 2007/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=34247098374&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34247098374&partnerID=8YFLogxK
U2 - 10.1089/ars.2006.1517
DO - 10.1089/ars.2006.1517
M3 - Article
C2 - 17465882
AN - SCOPUS:34247098374
VL - 9
SP - 597
EP - 601
JO - Antioxidants and Redox Signaling
JF - Antioxidants and Redox Signaling
SN - 1523-0864
IS - 5
ER -