New Insights into Oxidative Stress and Inflammatory Response in Neurodegenerative Diseases

Abstract

Oxidative stress (OS) and inflammation are two important and well-studied pathological hallmarks of neurodegenerative diseases (NDDs). Due to elevated oxygen consumption, the high presence of easily oxidizable polyunsaturated fatty acids and the weak antioxidant defenses, the brain is particularly vulnerable to oxidative injury. Uncertainty exists over whether these deficits contribute to the development of NDDs or are solely a consequence of neuronal degeneration. Furthermore, these two pathological hallmarks are linked, and it is known that OS can affect the inflammatory response. In this review, we will overview the last findings about these two pathways in the principal NDDs. Moreover, we will focus more in depth on amyotrophic lateral sclerosis (ALS) to understand how anti-inflammatory and antioxidants drugs have been used for the treatment of this still incurable motor neuron (MN) disease. Finally, we will analyze the principal past and actual clinical trials and the future perspectives in the study of these two pathological mechanisms.

Dynamics in Redox-Active Molecules Following Ischemic Preconditioning in the Brain

“…Since the brain has abundant lipid content, high energy requirements, and weak antioxidant capacity, it is an easy target for excessive oxidative insults [ 40 ]. Therefore, the brain even in basal conditions requires effective strategies to cope with oxidative stress, which ultimately leads to the modification of biomolecules such as proteins, which carry out the most essential cellular functions [ 40 , 41 , 42 ]. The proteome is highly dynamic and adapts in response to changes in the environment; therefore, its composition bears critical information related to the actual state of the organism.…”

The Vital Role of Melatonin and Its Metabolites in the Neuroprotection and Retardation of Brain Aging

“…Large amounts of oxidative stress are thought to be a major contributing factor in most neurodegenerative diseases, playing a role similar to its involvement in the process of brain aging [116,[132][133][134][135][136]. Oxidized proteins and lipid peroxidation were observed in patients with mild cognitive impairment and early stage Alzheimer's disease, which possibly precede Aβ accumulation [137].…”

The Role of Phospholipid Alterations in Mitochondrial and Brain Dysfunction after Cardiac Arrest

“…This has led to the belief that the phospholipid profile of the brain contains more PUFAs, such as 20:4 and 22:6, than other tissues [40,41]. As a result, it has previously been hypothesized that the abundance of these easily oxidized PUFAs is a major component in the susceptibility of the brain to ischemia/reperfusion injury [42]. However, when the phospholipid compositions of brain, heart, liver, and kidney tissues were compared in rats, brain tissue was actually revealed to contain a relatively higher concentration of MUFAs and saturated fatty acids and lower concentration of PUFAs.…”