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Role of upregulation of the K(ATP) channel subunit SUR1 in dopaminergic neuron degeneration in Parkinson’s disease
Accumulating evidence suggests that ATP‐sensitive potassium (K(ATP)) channels play an important role in the selective degeneration of dopaminergic neurons in the substantia nigra (SN). Furthermore, the expression of the K(ATP) channel subunit sulfonylurea receptor 1 (SUR1) is upregulated in the rema...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9124303/ https://www.ncbi.nlm.nih.gov/pubmed/35441806 http://dx.doi.org/10.1111/acel.13618 |
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author | Liu, Min Liu, Cui Xiao, Xue Han, Shuai‐Shuai Bi, Ming‐Xia Jiao, Qian Chen, Xi Yan, Chun‐Ling Du, Xi‐Xun Jiang, Hong |
author_facet | Liu, Min Liu, Cui Xiao, Xue Han, Shuai‐Shuai Bi, Ming‐Xia Jiao, Qian Chen, Xi Yan, Chun‐Ling Du, Xi‐Xun Jiang, Hong |
author_sort | Liu, Min |
collection | PubMed |
description | Accumulating evidence suggests that ATP‐sensitive potassium (K(ATP)) channels play an important role in the selective degeneration of dopaminergic neurons in the substantia nigra (SN). Furthermore, the expression of the K(ATP) channel subunit sulfonylurea receptor 1 (SUR1) is upregulated in the remaining nigral dopaminergic neurons in Parkinson's disease (PD). However, the mechanism underlying this selective upregulation of the SUR1 subunit and its subsequent roles in PD progression are largely unknown. In 3‐, 6‐, and 9‐month‐old A53T α‐synuclein transgenic (α‐SynA53T(+/+)) mice, only the SUR1 subunit and not SUR2B or Kir6.2 was upregulated, accompanied by neuronal damage. Moreover, the occurrence of burst firing in dopaminergic neurons was increased with the upregulation of the SUR1 subunit, whereas no changes in the firing rate were observed except in 9‐month‐old α‐SynA53T(+/+) mice. After interference with SUR1 expression by injection of lentivirus into the SN, the progression of dopaminergic neuron degeneration was delayed. Further studies showed that elevated expression of the transcription factors FOXA1 and FOXA2 could cause the upregulation of the SUR1 subunit in α‐SynA53T(+/+) mice. Our findings revealed the regulatory mechanism of the SUR1 subunit and the role of K(ATP) channels in the progression of dopaminergic neuron degeneration, providing a new target for PD drug therapy. |
format | Online Article Text |
id | pubmed-9124303 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-91243032022-05-24 Role of upregulation of the K(ATP) channel subunit SUR1 in dopaminergic neuron degeneration in Parkinson’s disease Liu, Min Liu, Cui Xiao, Xue Han, Shuai‐Shuai Bi, Ming‐Xia Jiao, Qian Chen, Xi Yan, Chun‐Ling Du, Xi‐Xun Jiang, Hong Aging Cell Research Articles Accumulating evidence suggests that ATP‐sensitive potassium (K(ATP)) channels play an important role in the selective degeneration of dopaminergic neurons in the substantia nigra (SN). Furthermore, the expression of the K(ATP) channel subunit sulfonylurea receptor 1 (SUR1) is upregulated in the remaining nigral dopaminergic neurons in Parkinson's disease (PD). However, the mechanism underlying this selective upregulation of the SUR1 subunit and its subsequent roles in PD progression are largely unknown. In 3‐, 6‐, and 9‐month‐old A53T α‐synuclein transgenic (α‐SynA53T(+/+)) mice, only the SUR1 subunit and not SUR2B or Kir6.2 was upregulated, accompanied by neuronal damage. Moreover, the occurrence of burst firing in dopaminergic neurons was increased with the upregulation of the SUR1 subunit, whereas no changes in the firing rate were observed except in 9‐month‐old α‐SynA53T(+/+) mice. After interference with SUR1 expression by injection of lentivirus into the SN, the progression of dopaminergic neuron degeneration was delayed. Further studies showed that elevated expression of the transcription factors FOXA1 and FOXA2 could cause the upregulation of the SUR1 subunit in α‐SynA53T(+/+) mice. Our findings revealed the regulatory mechanism of the SUR1 subunit and the role of K(ATP) channels in the progression of dopaminergic neuron degeneration, providing a new target for PD drug therapy. John Wiley and Sons Inc. 2022-04-20 2022-05 /pmc/articles/PMC9124303/ /pubmed/35441806 http://dx.doi.org/10.1111/acel.13618 Text en © 2022 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Liu, Min Liu, Cui Xiao, Xue Han, Shuai‐Shuai Bi, Ming‐Xia Jiao, Qian Chen, Xi Yan, Chun‐Ling Du, Xi‐Xun Jiang, Hong Role of upregulation of the K(ATP) channel subunit SUR1 in dopaminergic neuron degeneration in Parkinson’s disease |
title | Role of upregulation of the K(ATP) channel subunit SUR1 in dopaminergic neuron degeneration in Parkinson’s disease |
title_full | Role of upregulation of the K(ATP) channel subunit SUR1 in dopaminergic neuron degeneration in Parkinson’s disease |
title_fullStr | Role of upregulation of the K(ATP) channel subunit SUR1 in dopaminergic neuron degeneration in Parkinson’s disease |
title_full_unstemmed | Role of upregulation of the K(ATP) channel subunit SUR1 in dopaminergic neuron degeneration in Parkinson’s disease |
title_short | Role of upregulation of the K(ATP) channel subunit SUR1 in dopaminergic neuron degeneration in Parkinson’s disease |
title_sort | role of upregulation of the k(atp) channel subunit sur1 in dopaminergic neuron degeneration in parkinson’s disease |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9124303/ https://www.ncbi.nlm.nih.gov/pubmed/35441806 http://dx.doi.org/10.1111/acel.13618 |
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