Downregulation of dual-specificity phosphatase 1 (DUSP1) in post-mortem brain white matter in progressive multiple sclerosis

Martí Oró-Nolla; Melody Cui Sun; Thomas Reilly; Julia Anandarajah; Almudena Otálora-Alcaraz; Lisa Costelloe; Hugh Kearney; Richard Magee; Yvonne M Nolan; Eric J Downer

doi:10.1007/s10072-026-08944-2

Downregulation of dual-specificity phosphatase 1 (DUSP1) in post-mortem brain white matter in progressive multiple sclerosis

Martí Oró-Nolla
, Melody Cui Sun
, Thomas Reilly
, Julia Anandarajah
, Almudena Otálora-Alcaraz
, Lisa Costelloe
, Hugh Kearney
, Richard Magee
, Yvonne M Nolan
, Eric J Downer

School of Medicine

Trinity College Dublin
Beaumont Hospital
St James's Hospital
University College Cork

Research output: Contribution to journal › Article › peer-review

Abstract

OBJECTIVE: Dual-specificity phosphatase 1 (DUSP1) is a negative regulator of mitogen-activated protein kinase (MAPK) activity, and a player in the control of glial function. Several disease models have identified that the expression of DUSP1 is altered in tissue samples, which may contribute to disease pathogenesis. Using post-mortem brain tissue from a cohort of progressive multiple sclerosis (MS) cases, this study set out to determine if the expression of DUSP1 is altered in the brain in MS.

METHODS: We employed the use of a combination of PCR, western immunoblotting and immunohistochemical analysis to profile the expression of DUSP1.

RESULTS: Data presented herein indicate that DUSP1 is significantly downregulated at gene and protein level in MS white matter tissue, when compared to samples from a non-MS control cohort. We also identify that DUSP1 is expressed on Iba1 + cells in the brain and that ITGAM (CD11b) expression is elevated in white matter in progressive MS.

CONCLUSIONS: These findings provide evidence that DUSP1 is dysregulated centrally in CNS white matter in progressive MS.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10072-026-08944-2.

Original language	English
Journal	Neurological Sciences
Volume	47
Issue number	4
DOIs	https://doi.org/10.1007/s10072-026-08944-2
Publication status	Published - 12 Mar 2026

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@article{bac4829c80e24c338033e3098b240b2d,

title = "Downregulation of dual-specificity phosphatase 1 (DUSP1) in post-mortem brain white matter in progressive multiple sclerosis",

abstract = "OBJECTIVE: Dual-specificity phosphatase 1 (DUSP1) is a negative regulator of mitogen-activated protein kinase (MAPK) activity, and a player in the control of glial function. Several disease models have identified that the expression of DUSP1 is altered in tissue samples, which may contribute to disease pathogenesis. Using post-mortem brain tissue from a cohort of progressive multiple sclerosis (MS) cases, this study set out to determine if the expression of DUSP1 is altered in the brain in MS.METHODS: We employed the use of a combination of PCR, western immunoblotting and immunohistochemical analysis to profile the expression of DUSP1.RESULTS: Data presented herein indicate that DUSP1 is significantly downregulated at gene and protein level in MS white matter tissue, when compared to samples from a non-MS control cohort. We also identify that DUSP1 is expressed on Iba1 + cells in the brain and that ITGAM (CD11b) expression is elevated in white matter in progressive MS. CONCLUSIONS: These findings provide evidence that DUSP1 is dysregulated centrally in CNS white matter in progressive MS.SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10072-026-08944-2.",

author = "Mart{\'i} Or{\'o}-Nolla and Sun, \{Melody Cui\} and Thomas Reilly and Julia Anandarajah and Almudena Ot{\'a}lora-Alcaraz and Lisa Costelloe and Hugh Kearney and Richard Magee and Nolan, \{Yvonne M\} and Downer, \{Eric J\}",

year = "2026",

month = mar,

day = "12",

doi = "10.1007/s10072-026-08944-2",

language = "English",

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journal = "Neurological Sciences",

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T1 - Downregulation of dual-specificity phosphatase 1 (DUSP1) in post-mortem brain white matter in progressive multiple sclerosis

AU - Oró-Nolla, Martí

AU - Sun, Melody Cui

AU - Reilly, Thomas

AU - Anandarajah, Julia

AU - Otálora-Alcaraz, Almudena

AU - Costelloe, Lisa

AU - Kearney, Hugh

AU - Magee, Richard

AU - Nolan, Yvonne M

AU - Downer, Eric J

PY - 2026/3/12

Y1 - 2026/3/12

N2 - OBJECTIVE: Dual-specificity phosphatase 1 (DUSP1) is a negative regulator of mitogen-activated protein kinase (MAPK) activity, and a player in the control of glial function. Several disease models have identified that the expression of DUSP1 is altered in tissue samples, which may contribute to disease pathogenesis. Using post-mortem brain tissue from a cohort of progressive multiple sclerosis (MS) cases, this study set out to determine if the expression of DUSP1 is altered in the brain in MS.METHODS: We employed the use of a combination of PCR, western immunoblotting and immunohistochemical analysis to profile the expression of DUSP1.RESULTS: Data presented herein indicate that DUSP1 is significantly downregulated at gene and protein level in MS white matter tissue, when compared to samples from a non-MS control cohort. We also identify that DUSP1 is expressed on Iba1 + cells in the brain and that ITGAM (CD11b) expression is elevated in white matter in progressive MS. CONCLUSIONS: These findings provide evidence that DUSP1 is dysregulated centrally in CNS white matter in progressive MS.SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10072-026-08944-2.

AB - OBJECTIVE: Dual-specificity phosphatase 1 (DUSP1) is a negative regulator of mitogen-activated protein kinase (MAPK) activity, and a player in the control of glial function. Several disease models have identified that the expression of DUSP1 is altered in tissue samples, which may contribute to disease pathogenesis. Using post-mortem brain tissue from a cohort of progressive multiple sclerosis (MS) cases, this study set out to determine if the expression of DUSP1 is altered in the brain in MS.METHODS: We employed the use of a combination of PCR, western immunoblotting and immunohistochemical analysis to profile the expression of DUSP1.RESULTS: Data presented herein indicate that DUSP1 is significantly downregulated at gene and protein level in MS white matter tissue, when compared to samples from a non-MS control cohort. We also identify that DUSP1 is expressed on Iba1 + cells in the brain and that ITGAM (CD11b) expression is elevated in white matter in progressive MS. CONCLUSIONS: These findings provide evidence that DUSP1 is dysregulated centrally in CNS white matter in progressive MS.SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10072-026-08944-2.

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DO - 10.1007/s10072-026-08944-2

M3 - Article

C2 - 41814011

SN - 1590-1874

VL - 47

JO - Neurological Sciences

JF - Neurological Sciences

IS - 4

ER -

Downregulation of dual-specificity phosphatase 1 (DUSP1) in post-mortem brain white matter in progressive multiple sclerosis

Abstract

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