Intranasal interferon-beta as a promising alternative for the treatment of Alzheimer's disease

Chavoshinezhad, Sara; Safari, Vajihe; Izadpanah, Esmael

doi:10.1016/j.mehy.2022.110996

Cited by 4 publications

(2 citation statements)

References 64 publications

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“…While a previous study found that TSPO induces a retrograde mitochondrial-nuclear signalling via NF-kβ in breast cancer cell line survival (Desai et al ), our data suggests the age-dependent effects of TSPO on immune responses may be mediated via an effect on NF-kβ and interferon transcriptional pathways. Since NF-kβ and interferons have been identified as potential therapeutic targets in AD (Chavoshinezhad et al , 2023; Grimaldi et al , 2014; Mudò et al , 2019; Sun et al , 2022), this TSPO-aging interaction in NF-kβ and interferon transcriptional pathways may be an important consideration in therapeutic development.…”

Section: Resultsmentioning

confidence: 99%

Interaction between mitochondrial translocator protein and aging in inflammatory responses in mouse hippocampus

Lai,

Tham,

Fairley

et al. 2024

Preprint

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

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Section: Resultsmentioning

confidence: 99%

Interaction between mitochondrial translocator protein and aging in inflammatory responses in mouse hippocampus

Lai,

Tham,

Fairley

et al. 2024

Preprint

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“…Therefore, changes in cognitive ability in rats in this study are not only influenced by anesthetics but also related to the method of anesthesia. Ferroptosis is an iron-and ROS-dependent form of regulated cell death whose activation is thought to be responsible for neuronal cell death in neurodegenerative diseases [24], which is characterized by iron-dependent lipid peroxidation and implicated in neuroinflammation Propofol suppressed post-splenectomy ferroptosis in the hippocampus of aged rats. Iron deposition in the CA1 region (a).…”

Section: Discussionmentioning

confidence: 99%

Propofol ameliorates cognitive deficits following splenectomy in aged rats by inhibiting ferroptosis via the SIRT1/Nrf2/GPX4 pathway

Wen,

Zhang,

Wang

et al. 2024

NeuroReport

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The aim of this study was to investigate the mechanism by which propofol reduces postoperative cognitive dysfunction after splenectomy in aged rats. The rats in the model group and propofol group were subjected to splenectomy, and anesthetized with isoflurane and propofol, respectively. Utilizing the western blotting to assess the expression of sirtuin-1 (SIRT1) in the hippocampus. Molecular docking technology was used to predict the binding ability of propofol and SIRT1. Behavioral tests were performed using the Morris water maze, and the hippocampus was isolated for mechanistic investigations. Molecular docking showed that propofol and SIRT1 had a strong binding affinity. The expression of SIRT1 and its related proteins Nrf2, HO-1, NQO1, and GPX4 in the model rats was decreased compared with the sham group. Moreover, the model group exhibited cognitive decline, such as extended escape latency and decreased number of platform crossings. Pathological analysis showed that the number of apoptotic neurons, the levels of oxidative stress and neuroinflammation, the iron deposition, and the expressions of ACSL4 and TFR1 were increased, while the expressions of SLC7A11 and FTH1 were decreased in the hippocampal CA1 region within the model group. These pathological changes in the propofol group were, however, less than those in the model group. Nevertheless, the SIRT1 inhibitor increased these pathological changes compared with the propofol group. Compared with isoflurane, propofol inhibits ferroptosis in the hippocampus of splenectomized rats by causing less downregulation of the SIRT1/Nrf2/GPX4 pathway, thereby reducing the negative impact on cognitive function.

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The Overview of Drugs Used in Alzheimer’s Disease and Their Molecular Targets

Vishwas,

Gulati,

Babu

et al. 2023

Deciphering Drug Targets for Alzheimer’s Disease

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Intranasal interferon-beta as a promising alternative for the treatment of Alzheimer's disease

Cited by 4 publications

References 64 publications

Interaction between mitochondrial translocator protein and aging in inflammatory responses in mouse hippocampus

Interaction between mitochondrial translocator protein and aging in inflammatory responses in mouse hippocampus

Propofol ameliorates cognitive deficits following splenectomy in aged rats by inhibiting ferroptosis via the SIRT1/Nrf2/GPX4 pathway

The Overview of Drugs Used in Alzheimer’s Disease and Their Molecular Targets

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