Nonphosphorylated tau slows down Aβ1–42 aggregation, binds to Aβ1–42 oligomers, and reduces Aβ1–42 toxicity Article Swipe
Marten Beeg
,
Elisabetta Battocchio
,
Ada De Luigi
,
Laura Colombo
,
Carmina Natale
,
Alfredo Cagnotto
,
Alessandro Corbelli
,
Fabio Fiordaliso
,
Luisa Diomede
,
Mario Salmona
,
Marco Gobbi
·
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1016/j.jbc.2021.100664
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1016/j.jbc.2021.100664
The formation of neurofibrillary tangles and amyloid plaques accompanies the progression of Alzheimer's disease. Tangles are made of fibrillar aggregates formed by the microtubule-associated protein tau, whereas plaques comprise fibrillar forms of amyloid-beta (Aβ). Both form toxic oligomers during aggregation and are thought to interact synergistically to each promote the accumulation of the other. Recent in vitro studies have suggested that the monomeric nonphosphorylated full-length tau protein hinders the aggregation of Aβ1-40 peptide, but whether the same is true for the more aggregation-prone Aβ1-42 was not determined. We used in vitro and in vivo techniques to explore this question. We have monitored the aggregation kinetics of Aβ1-42 by thioflavine T fluorescence in the presence or the absence of different concentrations of nonphosphorylated tau. We observed that elongation of Aβ1-42 fibrils was inhibited by tau in a dose-dependent manner. Interestingly, the fibrils were structurally different in the presence of tau but did not incorporate tau. Surface plasmon resonance indicated that tau monomers bound to Aβ1-42 oligomers (but not monomers) and hindered their interaction with the anti-Aβ antibody 4G8, suggesting that tau binds to the hydrophobic central core of Aβ recognized by 4G8. Tau monomers also antagonized the toxic effects of Aβ oligomers in Caenorhabditis elegans. This suggests that nonphosphorylated tau might have a neuroprotective effect by binding Aβ1-42 oligomers formed during the aggregation and shielding their hydrophobic patches.
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- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1016/j.jbc.2021.100664
- http://www.jbc.org/article/S002192582100452X/pdf
- OA Status
- gold
- Cited By
- 6
- References
- 58
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3154065496
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W3154065496Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1016/j.jbc.2021.100664Digital Object Identifier
- Title
-
Nonphosphorylated tau slows down Aβ1–42 aggregation, binds to Aβ1–42 oligomers, and reduces Aβ1–42 toxicityWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2021Year of publication
- Publication date
-
2021-01-01Full publication date if available
- Authors
-
Marten Beeg, Elisabetta Battocchio, Ada De Luigi, Laura Colombo, Carmina Natale, Alfredo Cagnotto, Alessandro Corbelli, Fabio Fiordaliso, Luisa Diomede, Mario Salmona, Marco GobbiList of authors in order
- Landing page
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https://doi.org/10.1016/j.jbc.2021.100664Publisher landing page
- PDF URL
-
https://www.jbc.org/article/S002192582100452X/pdfDirect link to full text PDF
- Open access
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YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://www.jbc.org/article/S002192582100452X/pdfDirect OA link when available
- Concepts
-
Chemistry, Fibril, Monomer, Biophysics, Tau protein, Protein aggregation, Amyloid beta, Amyloid (mycology), In vitro, Peptide, Biochemistry, Alzheimer's disease, Biology, Polymer, Organic chemistry, Pathology, Medicine, Inorganic chemistry, DiseaseTop concepts (fields/topics) attached by OpenAlex
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6Total citation count in OpenAlex
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2025: 2, 2024: 1, 2022: 3Per-year citation counts (last 5 years)
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58Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.vivo | 93 |
| abstract_inverted_index.were | 141 |
| abstract_inverted_index.with | 172 |
| abstract_inverted_index.binds | 180 |
| abstract_inverted_index.bound | 161 |
| abstract_inverted_index.forms | 30 |
| abstract_inverted_index.might | 209 |
| abstract_inverted_index.their | 170, 224 |
| abstract_inverted_index.toxic | 36, 196 |
| abstract_inverted_index.vitro | 56, 90 |
| abstract_inverted_index.(Aβ). | 33 |
| abstract_inverted_index.Recent | 54 |
| abstract_inverted_index.during | 38, 219 |
| abstract_inverted_index.effect | 213 |
| abstract_inverted_index.formed | 20, 218 |
| abstract_inverted_index.other. | 53 |
| abstract_inverted_index.Surface | 154 |
| abstract_inverted_index.Tangles | 14 |
| abstract_inverted_index.absence | 116 |
| abstract_inverted_index.amyloid | 6 |
| abstract_inverted_index.binding | 215 |
| abstract_inverted_index.central | 184 |
| abstract_inverted_index.effects | 197 |
| abstract_inverted_index.explore | 96 |
| abstract_inverted_index.fibrils | 129, 140 |
| abstract_inverted_index.hinders | 67 |
| abstract_inverted_index.manner. | 137 |
| abstract_inverted_index.plaques | 7, 27 |
| abstract_inverted_index.plasmon | 155 |
| abstract_inverted_index.promote | 48 |
| abstract_inverted_index.protein | 24, 66 |
| abstract_inverted_index.studies | 57 |
| abstract_inverted_index.tangles | 4 |
| abstract_inverted_index.thought | 42 |
| abstract_inverted_index.whereas | 26 |
| abstract_inverted_index.whether | 74 |
| abstract_inverted_index.anti-Aβ | 174 |
| abstract_inverted_index.antibody | 175 |
| abstract_inverted_index.comprise | 28 |
| abstract_inverted_index.disease. | 13 |
| abstract_inverted_index.elegans. | 203 |
| abstract_inverted_index.hindered | 169 |
| abstract_inverted_index.interact | 44 |
| abstract_inverted_index.kinetics | 104 |
| abstract_inverted_index.monomers | 160, 192 |
| abstract_inverted_index.observed | 124 |
| abstract_inverted_index.patches. | 226 |
| abstract_inverted_index.peptide, | 72 |
| abstract_inverted_index.presence | 113, 146 |
| abstract_inverted_index.suggests | 205 |
| abstract_inverted_index.different | 118, 143 |
| abstract_inverted_index.fibrillar | 18, 29 |
| abstract_inverted_index.formation | 1 |
| abstract_inverted_index.indicated | 157 |
| abstract_inverted_index.inhibited | 131 |
| abstract_inverted_index.monitored | 101 |
| abstract_inverted_index.monomeric | 62 |
| abstract_inverted_index.monomers) | 167 |
| abstract_inverted_index.oligomers | 37, 164, 200, 217 |
| abstract_inverted_index.question. | 98 |
| abstract_inverted_index.resonance | 156 |
| abstract_inverted_index.shielding | 223 |
| abstract_inverted_index.suggested | 59 |
| abstract_inverted_index.aggregates | 19 |
| abstract_inverted_index.elongation | 126 |
| abstract_inverted_index.recognized | 188 |
| abstract_inverted_index.suggesting | 177 |
| abstract_inverted_index.techniques | 94 |
| abstract_inverted_index.Alzheimer's | 12 |
| abstract_inverted_index.accompanies | 8 |
| abstract_inverted_index.aggregation | 39, 69, 103, 221 |
| abstract_inverted_index.antagonized | 194 |
| abstract_inverted_index.determined. | 86 |
| abstract_inverted_index.full-length | 64 |
| abstract_inverted_index.hydrophobic | 183, 225 |
| abstract_inverted_index.incorporate | 152 |
| abstract_inverted_index.interaction | 171 |
| abstract_inverted_index.progression | 10 |
| abstract_inverted_index.thioflavine | 108 |
| abstract_inverted_index.accumulation | 50 |
| abstract_inverted_index.amyloid-beta | 32 |
| abstract_inverted_index.fluorescence | 110 |
| abstract_inverted_index.structurally | 142 |
| abstract_inverted_index.Caenorhabditis | 202 |
| abstract_inverted_index.Interestingly, | 138 |
| abstract_inverted_index.concentrations | 119 |
| abstract_inverted_index.dose-dependent | 136 |
| abstract_inverted_index.neurofibrillary | 3 |
| abstract_inverted_index.neuroprotective | 212 |
| abstract_inverted_index.synergistically | 45 |
| abstract_inverted_index.aggregation-prone | 82 |
| abstract_inverted_index.nonphosphorylated | 63, 121, 207 |
| abstract_inverted_index.Aβ<sub>1-40</sub> | 71 |
| abstract_inverted_index.Aβ<sub>1-42</sub> | 83, 106, 128, 163, 216 |
| abstract_inverted_index.microtubule-associated | 23 |
| cited_by_percentile_year.max | 97 |
| cited_by_percentile_year.min | 90 |
| corresponding_author_ids | https://openalex.org/A5007066407 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 11 |
| corresponding_institution_ids | https://openalex.org/I19630809 |
| citation_normalized_percentile.value | 0.62046432 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |