RT-QuIC Using C-Terminally Truncated α-Synuclein Forms Detects Differences in Seeding Propensity of Different Brain Regions from Synucleinopathies
<div><p>Aggregated α-synuclein (αSyn) protein is a core pathological feature of Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). Both PD and DLB demonstrate the presence of diverse intracellular α-synuclein (αSyn) species, including C-terminally truncated αSyn (C-αSyn), alth...
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2021
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| _version_ | 1864513515310546944 |
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| author | Ilaria Poggiolini (296742) |
| author2 | Daniel Erskine (3471959) Nishant N. Vaikath (2901785) Janarthanan Ponraj (8535585) Said Mansour (8697699) Christopher M. Morris (741292) Omar M. A. El-Agnaf (8809331) |
| author2_role | author author author author author author |
| author_facet | Ilaria Poggiolini (296742) Daniel Erskine (3471959) Nishant N. Vaikath (2901785) Janarthanan Ponraj (8535585) Said Mansour (8697699) Christopher M. Morris (741292) Omar M. A. El-Agnaf (8809331) |
| author_role | author |
| dc.creator.none.fl_str_mv | Ilaria Poggiolini (296742) Daniel Erskine (3471959) Nishant N. Vaikath (2901785) Janarthanan Ponraj (8535585) Said Mansour (8697699) Christopher M. Morris (741292) Omar M. A. El-Agnaf (8809331) |
| dc.date.none.fl_str_mv | 2021-05-31T03:00:00Z |
| dc.identifier.none.fl_str_mv | 10.3390/biom11060820 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/RT-QuIC_Using_C-Terminally_Truncated_-Synuclein_Forms_Detects_Differences_in_Seeding_Propensity_of_Different_Brain_Regions_from_Synucleinopathies/25878046 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biomedical and clinical sciences Neurosciences synucleinopathies Parkinson’s disease dementia with Lewy bodies RT-QuIC α-synuclein C-terminally truncated αSyn |
| dc.title.none.fl_str_mv | RT-QuIC Using C-Terminally Truncated α-Synuclein Forms Detects Differences in Seeding Propensity of Different Brain Regions from Synucleinopathies |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <div><p>Aggregated α-synuclein (αSyn) protein is a core pathological feature of Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). Both PD and DLB demonstrate the presence of diverse intracellular α-synuclein (αSyn) species, including C-terminally truncated αSyn (C-αSyn), although it is unknown how C-αSyn species contribute to disease progression. Using recombinant C-αSyn and PD and DLB brain lysates as seeds in the real-time quaking-induced conversion (RT-QuIC) assay, we explored how C-αSyn may be involved in disease stratification. Comparing the seeding activity of aqueous-soluble fractions to detergent-soluble fractions, and using αSyn 1-130 as substrate for the RT-QuIC assay, the temporal cortex seeds differentiated PD and DLB from healthy controls. In contrast to the temporal cortex, where PD and DLB could not be distinguished, αSyn 1-130 seeded by the detergent-soluble fractions from the PD frontal cortex demonstrated greater seeding efficiency compared to the DLB frontal cortex. Moreover, proteinase K-resistant (PKres) fragments from the RT-QuIC end products using C-αSyn 1-130 or C-αSyn 1-115 were more obvious in the frontal cortex compared to the temporal cortex. Morphological examinations of RT-QuIC end products showed differences in the size of the fibrils between C-αSyn 1-130 and C-αSyn 1-115, in agreement with the RT-QuIC results. These data show that C-αSyn species can distinguish PD from DLB and suggest diversity in αSyn species across these synucleinopathies, which could play a role in disease progression.</p><p> </p></div><h2>Other Information</h2> <p> Published in: Biomolecules<br> License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3390/biom11060820" target="_blank">https://dx.doi.org/10.3390/biom11060820</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_fec7b20df051f60ca54e6df1ca2a4834 |
| identifier_str_mv | 10.3390/biom11060820 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/25878046 |
| publishDate | 2021 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | RT-QuIC Using C-Terminally Truncated α-Synuclein Forms Detects Differences in Seeding Propensity of Different Brain Regions from SynucleinopathiesIlaria Poggiolini (296742)Daniel Erskine (3471959)Nishant N. Vaikath (2901785)Janarthanan Ponraj (8535585)Said Mansour (8697699)Christopher M. Morris (741292)Omar M. A. El-Agnaf (8809331)Biomedical and clinical sciencesNeurosciencessynucleinopathiesParkinson’s diseasedementia with Lewy bodiesRT-QuICα-synucleinC-terminally truncated αSyn<div><p>Aggregated α-synuclein (αSyn) protein is a core pathological feature of Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). Both PD and DLB demonstrate the presence of diverse intracellular α-synuclein (αSyn) species, including C-terminally truncated αSyn (C-αSyn), although it is unknown how C-αSyn species contribute to disease progression. Using recombinant C-αSyn and PD and DLB brain lysates as seeds in the real-time quaking-induced conversion (RT-QuIC) assay, we explored how C-αSyn may be involved in disease stratification. Comparing the seeding activity of aqueous-soluble fractions to detergent-soluble fractions, and using αSyn 1-130 as substrate for the RT-QuIC assay, the temporal cortex seeds differentiated PD and DLB from healthy controls. In contrast to the temporal cortex, where PD and DLB could not be distinguished, αSyn 1-130 seeded by the detergent-soluble fractions from the PD frontal cortex demonstrated greater seeding efficiency compared to the DLB frontal cortex. Moreover, proteinase K-resistant (PKres) fragments from the RT-QuIC end products using C-αSyn 1-130 or C-αSyn 1-115 were more obvious in the frontal cortex compared to the temporal cortex. Morphological examinations of RT-QuIC end products showed differences in the size of the fibrils between C-αSyn 1-130 and C-αSyn 1-115, in agreement with the RT-QuIC results. These data show that C-αSyn species can distinguish PD from DLB and suggest diversity in αSyn species across these synucleinopathies, which could play a role in disease progression.</p><p> </p></div><h2>Other Information</h2> <p> Published in: Biomolecules<br> License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3390/biom11060820" target="_blank">https://dx.doi.org/10.3390/biom11060820</a></p>2021-05-31T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.3390/biom11060820https://figshare.com/articles/journal_contribution/RT-QuIC_Using_C-Terminally_Truncated_-Synuclein_Forms_Detects_Differences_in_Seeding_Propensity_of_Different_Brain_Regions_from_Synucleinopathies/25878046CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/258780462021-05-31T03:00:00Z |
| spellingShingle | RT-QuIC Using C-Terminally Truncated α-Synuclein Forms Detects Differences in Seeding Propensity of Different Brain Regions from Synucleinopathies Ilaria Poggiolini (296742) Biomedical and clinical sciences Neurosciences synucleinopathies Parkinson’s disease dementia with Lewy bodies RT-QuIC α-synuclein C-terminally truncated αSyn |
| status_str | publishedVersion |
| title | RT-QuIC Using C-Terminally Truncated α-Synuclein Forms Detects Differences in Seeding Propensity of Different Brain Regions from Synucleinopathies |
| title_full | RT-QuIC Using C-Terminally Truncated α-Synuclein Forms Detects Differences in Seeding Propensity of Different Brain Regions from Synucleinopathies |
| title_fullStr | RT-QuIC Using C-Terminally Truncated α-Synuclein Forms Detects Differences in Seeding Propensity of Different Brain Regions from Synucleinopathies |
| title_full_unstemmed | RT-QuIC Using C-Terminally Truncated α-Synuclein Forms Detects Differences in Seeding Propensity of Different Brain Regions from Synucleinopathies |
| title_short | RT-QuIC Using C-Terminally Truncated α-Synuclein Forms Detects Differences in Seeding Propensity of Different Brain Regions from Synucleinopathies |
| title_sort | RT-QuIC Using C-Terminally Truncated α-Synuclein Forms Detects Differences in Seeding Propensity of Different Brain Regions from Synucleinopathies |
| topic | Biomedical and clinical sciences Neurosciences synucleinopathies Parkinson’s disease dementia with Lewy bodies RT-QuIC α-synuclein C-terminally truncated αSyn |