Progesterone exerts a neuroprotective action in a Parkinson’s disease human cell model through membrane progesterone receptor α (mPRα/PAQR7)
Parkinson’s disease (PD) is the second most common neurodegenerative disease worldwide, and current treatment options are unsatisfactory on the long term. Several studies suggest a potential neuroprotective action by female hormones, especially estrogens. The potential role of progestogens, however,...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-03-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2023.1125962/full |
| _version_ | 1811155509549465600 |
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| author | Luca F. Castelnovo Peter Thomas |
| author_facet | Luca F. Castelnovo Peter Thomas |
| author_sort | Luca F. Castelnovo |
| collection | DOAJ |
| description | Parkinson’s disease (PD) is the second most common neurodegenerative disease worldwide, and current treatment options are unsatisfactory on the long term. Several studies suggest a potential neuroprotective action by female hormones, especially estrogens. The potential role of progestogens, however, is less defined, and no studies have investigated the potential involvement of membrane progesterone receptors (mPRs). In the present study, the putative neuroprotective role for mPRs was investigated in SH-SY5Y cells, using two established pharmacological treatments for cellular PD models, 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenylpyridinium (MPP+). Our results show that both the physiologic agonist progesterone and the specific mPR agonist Org OD 02-0 were effective in reducing SH-SY5Y cell death induced by 6-OHDA and MPP+, whereas the nuclear PR agonist promegestone (R5020) and the GABAA receptor agonist muscimol were ineffective. Experiments performed with gene silencing technology and selective pharmacological agonists showed that mPRα is the isoform responsible for the neuroprotective effects we observed. Further experiments showed that the PI3K-AKT and MAP kinase signaling pathways are involved in the mPRα-mediated progestogen neuroprotective action in SH-SY5Y cells. These findings suggest that mPRα could play a neuroprotective role in PD pathology and may be a promising target for the development of therapeutic strategies for PD prevention or management. |
| first_indexed | 2024-04-10T04:34:12Z |
| format | Article |
| id | doaj.art-c3ad11a1d6554a4b98bb2acbd726ae14 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-04-10T04:34:12Z |
| publishDate | 2023-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-c3ad11a1d6554a4b98bb2acbd726ae142023-03-10T04:46:49ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-03-011410.3389/fendo.2023.11259621125962Progesterone exerts a neuroprotective action in a Parkinson’s disease human cell model through membrane progesterone receptor α (mPRα/PAQR7)Luca F. CastelnovoPeter ThomasParkinson’s disease (PD) is the second most common neurodegenerative disease worldwide, and current treatment options are unsatisfactory on the long term. Several studies suggest a potential neuroprotective action by female hormones, especially estrogens. The potential role of progestogens, however, is less defined, and no studies have investigated the potential involvement of membrane progesterone receptors (mPRs). In the present study, the putative neuroprotective role for mPRs was investigated in SH-SY5Y cells, using two established pharmacological treatments for cellular PD models, 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenylpyridinium (MPP+). Our results show that both the physiologic agonist progesterone and the specific mPR agonist Org OD 02-0 were effective in reducing SH-SY5Y cell death induced by 6-OHDA and MPP+, whereas the nuclear PR agonist promegestone (R5020) and the GABAA receptor agonist muscimol were ineffective. Experiments performed with gene silencing technology and selective pharmacological agonists showed that mPRα is the isoform responsible for the neuroprotective effects we observed. Further experiments showed that the PI3K-AKT and MAP kinase signaling pathways are involved in the mPRα-mediated progestogen neuroprotective action in SH-SY5Y cells. These findings suggest that mPRα could play a neuroprotective role in PD pathology and may be a promising target for the development of therapeutic strategies for PD prevention or management.https://www.frontiersin.org/articles/10.3389/fendo.2023.1125962/fullParkinson’s diseasemembrane progesterone receptor αneuroprotectionPI3K-AKTERK |
| spellingShingle | Luca F. Castelnovo Peter Thomas Progesterone exerts a neuroprotective action in a Parkinson’s disease human cell model through membrane progesterone receptor α (mPRα/PAQR7) Frontiers in Endocrinology Parkinson’s disease membrane progesterone receptor α neuroprotection PI3K-AKT ERK |
| title | Progesterone exerts a neuroprotective action in a Parkinson’s disease human cell model through membrane progesterone receptor α (mPRα/PAQR7) |
| title_full | Progesterone exerts a neuroprotective action in a Parkinson’s disease human cell model through membrane progesterone receptor α (mPRα/PAQR7) |
| title_fullStr | Progesterone exerts a neuroprotective action in a Parkinson’s disease human cell model through membrane progesterone receptor α (mPRα/PAQR7) |
| title_full_unstemmed | Progesterone exerts a neuroprotective action in a Parkinson’s disease human cell model through membrane progesterone receptor α (mPRα/PAQR7) |
| title_short | Progesterone exerts a neuroprotective action in a Parkinson’s disease human cell model through membrane progesterone receptor α (mPRα/PAQR7) |
| title_sort | progesterone exerts a neuroprotective action in a parkinson s disease human cell model through membrane progesterone receptor α mprα paqr7 |
| topic | Parkinson’s disease membrane progesterone receptor α neuroprotection PI3K-AKT ERK |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2023.1125962/full |
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