Don't die like me: Which proteins are responsible for the selective neuronal vulnerability within the substantia nigra?
A hallmark of Parkinson's disease is the specific degeneration of dopaminergic neurons in the substantia nigra pars compacta. Interestingly, not all of these neurons are affected to the same extent. Studies revealed that neurons located more ventrally within the substantia nigra pars compacta h...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2024-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0296730 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841533122412281856 |
|---|---|
| author | Simone Steinbach Mariana Molina Lea T Grinberg Luisa Aring Annika Guntermann Katrin Marcus Helmut Heinsen Renata E Paraizo Leite Caroline May |
| author_facet | Simone Steinbach Mariana Molina Lea T Grinberg Luisa Aring Annika Guntermann Katrin Marcus Helmut Heinsen Renata E Paraizo Leite Caroline May |
| author_sort | Simone Steinbach |
| collection | DOAJ |
| description | A hallmark of Parkinson's disease is the specific degeneration of dopaminergic neurons in the substantia nigra pars compacta. Interestingly, not all of these neurons are affected to the same extent. Studies revealed that neurons located more ventrally within the substantia nigra pars compacta have a higher prevalence to degenerate than those located in the dorsal tier. The underlying reasons for this selective neuronal vulnerability are still unknown. The aim of the present study was to gain a better understanding of molecular differences between these two neuronal subpopulations that may explain the selective neuronal vulnerability within the human substantia nigra. For this purpose, the neurons from the ventral as well as dorsal tier of the substantia nigra were specifically isolated out of neuropathologically unremarkable human substantia nigra sections with laser microdissection. Following, their proteome was analyzed by data independent acquisition mass spectrometry. The samples were analysed donor-specifically and not pooled for this purpose. A total of 5,391 proteins were identified in the substantia nigra. Of these, 2,453 proteins could be quantified in 100% of the dorsal tier samples. 1,629 could be quantified in 100% of the ventral tier samples. Nine proteins were differentially regulated with a log2 value ≥0.5 and a Qvalue ≤0.05. Of these 7 were higher abundant in the dorsal tier and 2 higher in the ventral tier. These proteins are associated with the cytoskeleton, neuronal plasticity, or calcium homeostasis. With these findings a deeper understanding can be gained of the selective neuronal vulnerability within the substantia nigra and of protective mechanisms against neurodegeneration in specific neuronal subpopulations. |
| format | Article |
| id | doaj-art-c8e5c7a6e8da40168abe375de7542998 |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2024-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-c8e5c7a6e8da40168abe375de75429982025-01-17T05:32:01ZengPublic Library of Science (PLoS)PLoS ONE1932-62032024-01-01197e029673010.1371/journal.pone.0296730Don't die like me: Which proteins are responsible for the selective neuronal vulnerability within the substantia nigra?Simone SteinbachMariana MolinaLea T GrinbergLuisa AringAnnika GuntermannKatrin MarcusHelmut HeinsenRenata E Paraizo LeiteCaroline MayA hallmark of Parkinson's disease is the specific degeneration of dopaminergic neurons in the substantia nigra pars compacta. Interestingly, not all of these neurons are affected to the same extent. Studies revealed that neurons located more ventrally within the substantia nigra pars compacta have a higher prevalence to degenerate than those located in the dorsal tier. The underlying reasons for this selective neuronal vulnerability are still unknown. The aim of the present study was to gain a better understanding of molecular differences between these two neuronal subpopulations that may explain the selective neuronal vulnerability within the human substantia nigra. For this purpose, the neurons from the ventral as well as dorsal tier of the substantia nigra were specifically isolated out of neuropathologically unremarkable human substantia nigra sections with laser microdissection. Following, their proteome was analyzed by data independent acquisition mass spectrometry. The samples were analysed donor-specifically and not pooled for this purpose. A total of 5,391 proteins were identified in the substantia nigra. Of these, 2,453 proteins could be quantified in 100% of the dorsal tier samples. 1,629 could be quantified in 100% of the ventral tier samples. Nine proteins were differentially regulated with a log2 value ≥0.5 and a Qvalue ≤0.05. Of these 7 were higher abundant in the dorsal tier and 2 higher in the ventral tier. These proteins are associated with the cytoskeleton, neuronal plasticity, or calcium homeostasis. With these findings a deeper understanding can be gained of the selective neuronal vulnerability within the substantia nigra and of protective mechanisms against neurodegeneration in specific neuronal subpopulations.https://doi.org/10.1371/journal.pone.0296730 |
| spellingShingle | Simone Steinbach Mariana Molina Lea T Grinberg Luisa Aring Annika Guntermann Katrin Marcus Helmut Heinsen Renata E Paraizo Leite Caroline May Don't die like me: Which proteins are responsible for the selective neuronal vulnerability within the substantia nigra? PLoS ONE |
| title | Don't die like me: Which proteins are responsible for the selective neuronal vulnerability within the substantia nigra? |
| title_full | Don't die like me: Which proteins are responsible for the selective neuronal vulnerability within the substantia nigra? |
| title_fullStr | Don't die like me: Which proteins are responsible for the selective neuronal vulnerability within the substantia nigra? |
| title_full_unstemmed | Don't die like me: Which proteins are responsible for the selective neuronal vulnerability within the substantia nigra? |
| title_short | Don't die like me: Which proteins are responsible for the selective neuronal vulnerability within the substantia nigra? |
| title_sort | don t die like me which proteins are responsible for the selective neuronal vulnerability within the substantia nigra |
| url | https://doi.org/10.1371/journal.pone.0296730 |
| work_keys_str_mv | AT simonesteinbach dontdielikemewhichproteinsareresponsiblefortheselectiveneuronalvulnerabilitywithinthesubstantianigra AT marianamolina dontdielikemewhichproteinsareresponsiblefortheselectiveneuronalvulnerabilitywithinthesubstantianigra AT leatgrinberg dontdielikemewhichproteinsareresponsiblefortheselectiveneuronalvulnerabilitywithinthesubstantianigra AT luisaaring dontdielikemewhichproteinsareresponsiblefortheselectiveneuronalvulnerabilitywithinthesubstantianigra AT annikaguntermann dontdielikemewhichproteinsareresponsiblefortheselectiveneuronalvulnerabilitywithinthesubstantianigra AT katrinmarcus dontdielikemewhichproteinsareresponsiblefortheselectiveneuronalvulnerabilitywithinthesubstantianigra AT helmutheinsen dontdielikemewhichproteinsareresponsiblefortheselectiveneuronalvulnerabilitywithinthesubstantianigra AT renataeparaizoleite dontdielikemewhichproteinsareresponsiblefortheselectiveneuronalvulnerabilitywithinthesubstantianigra AT carolinemay dontdielikemewhichproteinsareresponsiblefortheselectiveneuronalvulnerabilitywithinthesubstantianigra |