Abstract
Neurodegenerative diseases (NDs) represents debilitating conditions characterized by degeneration of neuronal cells in specific brain areas, causing disability and death in patients. In the pathophysiology of NDs, oxidative stress, apoptosis and neuroinflammation have a key role, as demonstrated by in vivo and in vitro models. Therefore, the use of molecules with antioxidant and anti-inflammatory activities represents a possible strategy for the treatment of NDs. Many studies demonstrated the beneficial effects of fumaric acid esters (FAEs) to counteract neuroinflammation and oxidative stress. Among these molecules, dimethyl fumarate (DMF) showed a valid therapeutic approach to slow down neurodegeneration and relieve symptoms in patients with NDs. DMF is a methyl ester of fumaric acid and acts as modulator of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway as well as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) translocation. Therefore, this review aims to examine the potential beneficial effects of DMF to counteract oxidative stress and inflammation in patients with NDs.
Highlights
Neurodegenerative diseases (NDs) are debilitating conditions caused by the progressive degeneration and death of neurons; the prevalence of these diseases is rising in today’s society [1].NDs include a large spectrum of heterogeneous and multifactorial pathologies as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS). some genetic factors have been identified, the pathophysiology of NDs remains poorly understood [2]
The c-Rel protein is a transcriptional regulator for mitochondrial antioxidant and antiapoptotic factors, the reduction of its physiological production could contribute to oxidative stress (OS) in PD [77]; while mutations of the LLRK2 enzyme in PD would seem related to mitochondrial reactive oxygen species (ROS) production, suggesting the involvement of this enzyme in the regulation of OS and mitochondrial dysfunction [78]
dimethyl fumarate (DMF) represents a promising molecule in the management of many neurodegenerative diseases, thanks to its antioxidant, anti-inflammatory, immunomodulating, and neuroprotective properties
Summary
Neurodegenerative diseases (NDs) are debilitating conditions caused by the progressive degeneration and death of neurons; the prevalence of these diseases is rising in today’s society [1]. The molecular mechanisms of OS include inflammation, mitochondrial dysfunction, and apoptosis that culminates in neuronal death [6]. Nrf2-dependent genes are preferentially activated in astrocytes, providing an interesting cellular and molecular link between astrocyte dysfunction and the role of oxidative stress in neurodegeneration [8]. Many papers highlighted the importance of molecules with antioxidant activities for the treatment of NDs, such as the fumaric acid esters (FAEs), where DMF represents the most pharmacologically effective molecule [10]. DMF acts as an Nrf activator, able to stimulate a cellular defense to protect neurons from ROS-induced damage [11]. This review aims to highlight the involvement of OS in neurodegenerative diseases and the effect of DMF in the treatment of these diseases
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