Interaction between mitochondrial translocator protein and aging in inflammatory responses in mouse hippocampus DOI Open Access
Kei Onn Lai,

Nevin Tham,

Lauren H. Fairley

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 22, 2024

Abstract The mitochondrial translocator protein (TSPO) is a biomarker of inflammation which upregulated in the brain aging and associated neurodegenerative diseases, such as Alzheimer’s disease (AD). Here we investigated interaction between TSPO immunomodulatory function mouse hippocampus, region severely affected AD. Aging resulted reversal knockout transcriptional signatures following inflammatory insult, with deletion drastically exacerbating responses hippocampus whilst dampening young hippocampus. Drugs that disrupt cell cycle induce DNA-damage heat shock topoisomerase inhibitors were identified to mimic signature characterizing TSPO-dependent most closely. This TSPO-aging an important consideration interpretation TSPO-targeted therapeutic studies, well vitro studies cannot model brain.

Language: Английский

Age‐Dependent Regulation of Hippocampal Inflammation by the Mitochondrial Translocator Protein in Mice DOI Creative Commons
Kei Onn Lai, Jia Hui Wong,

Nevin Tham

et al.

Aging Cell, Journal Year: 2025, Volume and Issue: unknown

Published: April 24, 2025

ABSTRACT The mitochondrial translocator protein (TSPO) is a biomarker of inflammation associated with neurodegenerative diseases, widely regarded to be upregulated in the aging brain. Here we investigated interaction between and TSPO immunomodulatory function mouse hippocampus, region severely affected Alzheimer's Disease (AD). Surprisingly, found that levels were decreased brain innate immune populations aging. Aging resulted reversal knockout transcriptional signatures following inflammatory insult. deletion drastically exacerbated responses while dampening young hippocampus. This age‐dependent effect was linked NF‐kβ interferon regulatory networks. Drugs disrupt cell cycle induce DNA damage, such as heat shock topoisomerase inhibitors, identified mimic signature characterizing mice most closely. These findings indicate plays protective role TSPO–aging an important consideration interpretation TSPO‐targeted therapeutic studies, well vitro studies cannot model

Language: Английский

Citations

0
Translocator protein (TSPO), still an enigmatic transmembrane protein: from structures to functions DOI
J Lacapère, Vassilios Papadopoulos

Biochimie, Journal Year: 2024, Volume and Issue: 224, P. 1 - 2

Published: July 26, 2024

Language: Английский

Citations

1
Animal models of neuropathic pain DOI
Angela Maria Casaril,

Caitlyn M. Gaffney,

Andrew J. Shepherd

et al.

International review of neurobiology, Journal Year: 2024, Volume and Issue: unknown, P. 339 - 401

Published: Jan. 1, 2024

Language: Английский

Citations

1
Interaction between mitochondrial translocator protein and aging in inflammatory responses in mouse hippocampus DOI Open Access
Kei Onn Lai,

Nevin Tham,

Lauren H. Fairley

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 22, 2024

Abstract The mitochondrial translocator protein (TSPO) is a biomarker of inflammation which upregulated in the brain aging and associated neurodegenerative diseases, such as Alzheimer’s disease (AD). Here we investigated interaction between TSPO immunomodulatory function mouse hippocampus, region severely affected AD. Aging resulted reversal knockout transcriptional signatures following inflammatory insult, with deletion drastically exacerbating responses hippocampus whilst dampening young hippocampus. Drugs that disrupt cell cycle induce DNA-damage heat shock topoisomerase inhibitors were identified to mimic signature characterizing TSPO-dependent most closely. This TSPO-aging an important consideration interpretation TSPO-targeted therapeutic studies, well vitro studies cannot model brain.

Language: Английский

Citations

0