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41/100

✓ Peer-reviewed alzhub usefulness score 41 out of 100. Disease mechanisms

Topic: Disease mechanisms in lab and animal studies

Plain-language summary

Stress proteins located in the cytosol or endoplasmic reticulum (ER) maintain cell homeostasis and afford tolerance to severe insults. In neurodegenerative diseases, several chaperones ameliorate the accumulation of misfolded proteins triggered by oxidative or nitrosative stress, or of mutated gene products. Although severe ER stress can induce apoptosis, the ER withstands relatively mild insults through the expression of stress proteins or chaperones such as glucose-regulated protein (GRP) and protein-disulphide isomerase (PDI), which assist in the maturation and transport of unfolded secretory proteins. PDI catalyses thiol-disulphide exchange, thus facilitating disulphide bond formation and rearrangement reactions. PDI has two domains that function as independent active sites with homology to the small, redox-active protein thioredoxin. During neurodegenerative disorders and cerebral ischaemia, the accumulation of immature and denatured proteins results in ER dysfunction, but the upregulation of PDI represents an adaptive response to protect neuronal cells. Here we show, in brains manifesting sporadic Parkinson's or Alzheimer's disease, that PDI is S-nitrosylated, a reaction transferring a nitric oxide (NO) group to a critical cysteine thiol to affect protein function. NO-induced S-nitrosylation of PDI inhibits its enzymatic activity, leads to the accumulation of polyubiquitinated proteins, and activates the unfolded protein response. S-nitrosylation also abrogates PDI-mediated attenuation of neuronal cell death triggered by ER stress, misfolded proteins or proteasome inhibition. Thus, PDI prevents neurotoxicity associated with ER stress and protein misfolding, but NO blocks this protective effect in neurodegenerative disorders through the S-nitrosylation of PDI.

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APA 7th

Uehara, T., Nakamura, T., Yao, D., Shi, Z. Q., Gu, Z., Ma, Y., et al. (2006). S-nitrosylated protein-disulphide isomerase links protein misfolding to neurodegeneration. Nature. https://doi.org/10.1038/nature04782

Vancouver

Uehara T, Nakamura T, Yao D, Shi ZQ, Gu Z, Ma Y, et al. S-nitrosylated protein-disulphide isomerase links protein misfolding to neurodegeneration. Nature. 2006. doi:10.1038/nature04782. PMID: 16724068.

BibTeX

@article{uehara2006-16724068,
  author  = {Uehara, T. and Nakamura, T. and Yao, D. and Shi, Z. Q. and Gu, Z. and Ma, Y. and Masliah, E. and Nomura, Y. and others},
  title   = {{S-nitrosylated protein-disulphide isomerase links protein misfolding to neurodegeneration}},
  journal = {Nature},
  year    = {2006},
  doi     = {10.1038/nature04782},
  pmid    = {16724068},
  url     = {https://doi.org/10.1038/nature04782}
}

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Key findings

During neurodegenerative disorders and cerebral ischaemia, the accumulation of immature and denatured proteins results in ER dysfunction, but the upregulation of PDI represents an adaptive response to protect neuronal cells.
Thus, PDI prevents neurotoxicity associated with ER stress and protein misfolding, but NO blocks this protective effect in neurodegenerative disorders through the S-nitrosylation of PDI.

Study details

Evidence strengthLow

How this study scored 41/100

Published in a top-tier journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multicenter collaboration, so those were left out: it earned 24 of the 58 points we could judge it on, which is 41 out of 100.

Component	Points	Why
Journal tier	10 / 10	Tier 1 — top-tier general journal (Nature)
Journal's citation record	— / 4	No journal record from OpenAlex — left out of this score
Study design	0 / 12	No study design recorded — scores zero, not guessed (not stated in the record — scored 0)
Strength of evidence	1 / 5	Rated “low” in our summary
Peer-review validation	10 / 10	Peer-reviewed. Published as an article in a named peer-reviewed journal.
How recent	1 / 5	2006 — older than 20 years, still counted
Sample size	0 / 4	Participant count not stated — scores zero (not stated in the record — scored 0)
Effect reported	0 / 3	No effect size reported — scores zero (not stated in the record — scored 0)
Studied in people	0 / 3	Not stated whether this was studied in people — scores zero (not stated in the record — scored 0)
Randomized / blinded	0 / 2	No randomization or blinding stated — scores zero (not stated in the record — scored 0)
Times cited	— / 7	No citation count (not found in OpenAlex) — left out of this score
Citations per year	— / 5	No citation count or no year — left out of this score
Impact for its field and year	— / 6	No field-weighted citation impact (OpenAlex has none yet) — left out of this score
Cited by studies here	— / 6	Not yet checked against this library's citation graph — left out of this score
Still being cited	— / 4	No yearly citation counts — left out of this score
Senior author's track record	— / 4	Senior author's record not available — left out of this score
Institution's track record	— / 3	No institution listed in OpenAlex — left out of this score
Multicenter collaboration	— / 3	Institutions not listed — left out of this score
Indexed in PubMed	2 / 2	Indexed in PubMed (PMID 16724068)
Free to read	0 / 2	Behind a paywall — scores zero
Points	24 / 58	Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 24 of the 58 points we could judge it on is 41 out of 100.
Total	41 / 100	—

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