In FUS[1−359]‐tg mice O,S-dibenzoyl thiamine reduces muscle atrophy, decreases glycogen synthase kinase 3 beta, and normalizes the metabolome

Atualizações Em Promoção Da Saúde

“…No que diz respeito ao estresse oxidativo e antioxidantes, há indícios de que a a doença esteja associada a um desequilíbrio entre a produção de radicais livres e a capacidade antioxidante do organismo para neutralizá-los, resultando em danos às células nervosas e contribuindo para o progresso da patologia (Probert et al, 2022). Essa relação entre o estresse oxidativo e os antioxidantes sugere a importância de estratégias terapêuticas para fortalecer os sistemas antioxidantes naturais do corpo ou administrar antioxidantes exógenos para reduzir o estresse oxidativo e, consequentemente, diminuir o impacto negativo na patologia (Stella et al, 2021;Probert et al, 2022;Saiswaroop et al, 2023).…”

Lipopolysaccharide triggers exacerbated microglial activation, excessive cytokine release and behavioural disturbances in mice with truncated Fused-in-Sarcoma Protein (FUS)

“…The behavioural experiments were performed as described elsewhere ( de Munter et al, 2020a , 2020b ; Probert et al, 2022 ; Strekalova and Steinbusch, 2010 ; Strekalova et al, 2022a , Strekalova et al, 2022b ) ( see SF ).…”

“…However, little is known about an interaction of pre-existing pro-inflammatory conditions with an aberrant immune response in genetically determined FTLD and ALS syndromes such as the FUS mutations. Here, we used the FUS[1–359]-tg mouse line, expressing a truncated highly-aggregate-prone form of human FUS, which displays FTLD-like and ALS-like disease halmarks in both pre-symptomatic and symptomatic stages at 8 and 14 weeks respectively ( de Munter et al, 2020a , 2020b ; Probert et al, 2022 ; Sambon et al, 2020 ; Shelkovnikova et al, 2013 ), in conjunction with a systemic lipopolysaccharide (LPS) challenge.…”

“…Earlier studies with the FUS[1–359]-tg mice revealed that the pathology is associated with over-expression of the pro-inflammatory cytokines IL-1β and IL-6 in the brain, blood and spinal cord, and behavioural deficits in the symptomatic FUS[1–359]-tg mice ( de Munter et al, 2020a , 2020b ; Probert et al, 2022 ; Lysikova et al, 2019 ). However, gene expression studies failed to reveal any signs of altered microglial function or of inflammatory markers in the CNS of naïve pre-symptomatic FUS[1–359]-tg mice ( Chaprov et al, 2021 ).…”

Synthetic Thioesters of Thiamine: Promising Tools for Slowing Progression of Neurodegenerative Diseases

“…Two recent clinical studies suggested that a thiamine prodrug, benfotiamine (BFT), might be helpful in slowing down the evolution of Alzheimer's disease [13,14]. While many studies showed beneficial pharmacological effects of BFT in mouse models of neurodegenerative diseases [15][16][17], the mechanism of action is rarely discussed in terms of active metabolites and their molecular targets. In this review, after a brief introduction to the biochemical properties of thiamine and homeostasis, we will summarize the information available on the possible molecular targets of BFT and other thiamine prodrugs, as well as the possible metabolites involved.…”