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Characterization of hydrophobic residue requirements for alpha-synuclein fibrillization
Waxman EA, Mazzulli JR, Giasson BI.. Biochemistry, 2009-10-01
Topic: Brain proteins, microglia and lab models
alpha-Synuclein is the major component of pathological inclusions characteristic of diseases like Parkinson's disease, dementia with Lewy bodies, and multiple-system atrophy. A role for alpha-synuclein in neurodegenerative diseases is further supported by point mutations and duplication and triplication of the alpha-synuclein gene (SNCA) that are causative of these disorders. The middle hydrophobic region of the alpha-synuclein protein, also termed the "non-Abeta component of Alzheimer's disease amyloid plaque (NAC)" domain, is required for alpha-synuclein to polymerize into amyloid filaments, which are the major components of alpha-synuclein pathological inclusions. In this study, we assessed the importance of specific stretches of hydrophobic residues in driving the intrinsic ability of alpha-synuclein to polymerize. Several small deletions, even one with as few as two amino acid residues (A76 and V77), dramatically impaired the ability of alpha-synuclein to polymerize into mature amyloidogenic fibrils, and instead, it preferentially formed oligomers. However, this inhibition of filament assembly was clearly dependent on the spatial context, since similar and larger hydrophobic deletions in other parts of the NAC domain reduced only the rate of fibril formation, without abrogating filament assembly. Further, mutation of residue E83 to an A rescued the ability of mutant Delta76-77 alpha-synuclein to polymerize. These findings support the notion that while both the location and hydrophobicity of protein segments are important elements that affect the propensity to form amyloid fibrils, the intrinsic ability of a polypeptide to fold structurally into amyloid is also critical.
Key findings
- These findings support the notion that while both the location and hydrophobicity of protein segments are important elements that affect the propensity to form amyloid fibrils, the intrinsic ability of a polypeptide to fold structurally into amyloid is also critical.
Study details
- Evidence strengthLow
How this study scored 36/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / 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 multi-centre collaboration, so those were left out: it earned 21 of the 58 points we could judge it on, which is 36 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Biochemistry) |
| 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 | 2009 — within 20 year(s) of the newest study here |
| 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) |
| Randomised / blinded | 0 / 2 | No randomisation 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 |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 19722699) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 21 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 21 of the 58 points we could judge it on is 36 out of 100. |
| Total | 36 / 100 | — |
What each of these 20 components measures, and what this score is not →
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
APA 7th
Waxman, E. A., Mazzulli, JR., & Giasson, B. I. (2009). Characterization of hydrophobic residue requirements for alpha-synuclein fibrillization. Biochemistry. https://doi.org/10.1021/bi900539p
Vancouver
Waxman EA, Mazzulli JR, Giasson BI. Characterization of hydrophobic residue requirements for alpha-synuclein fibrillization. Biochemistry. 2009. doi:10.1021/bi900539p. PMID: 19722699.
BibTeX
@article{waxman2009-19722699,
author = {Waxman, E. A. and Mazzulli, JR. and Giasson, B. I.},
title = {{Characterization of hydrophobic residue requirements for alpha-synuclein fibrillization}},
journal = {Biochemistry},
year = {2009},
doi = {10.1021/bi900539p},
pmid = {19722699},
url = {https://doi.org/10.1021/bi900539p}
}
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