Fenamates as Potential Therapeutics for Neurodegenerative Disorders

Abstract

Neurodegenerative disorders are desperately lacking treatment options. It is imperative that drug repurposing be considered in the fight against neurodegenerative diseases. Fenamates have been studied for efficacy in treating several neurodegenerative diseases. The purpose of this review is to comprehensively present the past and current research on fenamates in the context of neurodegenerative diseases with a special emphasis on tolfenamic acid and Alzheimer’s disease. Furthermore, this review discusses the major molecular pathways modulated by fenamates.

Microglia as a cellular target of diclofenac therapy in Alzheimer’s disease

“… 7 In addition, in the United States, fenamates were primarily prescribed for menstrual symptoms in women below the age of 50 years, who have a low likelihood to develop AD. 7 , 122 Recent data in cell and animal models as well as in large epidemiological studies suggest diclofenac and fenamates as promising candidates to modify AD progression due to their unique pharmacological properties on the NLRP3/ IL-1β pathway ( Figure 2 ). Other mechanisms and pathways such as enhancement of transcription factor SP1 degradation and attenuation of peripheral inflammation could play a role as well, albeit pending further investigation ( Figure 2 ).…”

Druggable targets for the immunopathy of Alzheimer's disease

“…In a mouse model of AD, fenamate NSAIDs inhibited cognitive impairment and demonstrated both protective and therapeutic efficacies. 57 Diclofenac, a structurally related NSAID, was similarly shown to reduce levels of IL-1β. 58…”

“…In a mouse model of AD, fenamate NSAIDs inhibited cognitive impairment and demonstrated both protective and therapeutic efficacies. 57 Diclofenac, a structurally related NSAID, was similarly shown to reduce levels of IL-1β. 58 Structurally simpler molecules, such as endogenous β-hydroxybutyrate or the synthetic β-sulfonyl nitrile compound dapansutrile have demonstrated some efficacy in AD models as well (Fig.…”

Meclofenamate Suppresses MUC5AC Mucin Gene Expression by Regulating the NF-kB Signaling Pathway in Human Pulmonary Mucoepidermoid NCI-H292 Cells

“…Meclofenamate was previously utilized to ameliorate psoriatic arthritis ( Ellis et al ., 1986 ), treat a specific type of severe nephrotic syndrome ( Velosa et al ., 1985 ), and regulate parasitic infection by hookworm ( Cho et al ., 2011 ). Meclofenamate can be used as an anticancer agent for small cell lung carcinoma and prostate cancer ( Chen et al ., 2022 ; Saglam et al ., 2022 ; Yanar et al ., 2022 ), and could be employed as a therapeutic agent for neurodegenerative disorders ( Hill and Zawia, 2021 ). However, there are no reports on the effect of meclofenamate on mucin gene expression in airway epithelial cells.…”