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.

Keywords: amyotrophic lateral sclerosis; inflammation; neurodegenerative diseases; oxidative stress; reactive oxygen species.

Figure 1

Redox balance and imbalance in organisms. (a) The redox balance in living organisms is maintained by the equilibrium between reactive oxygen species (ROS) levels and the action of antioxidants. O²⁻ = superoxide anions, OH = hydroxyl radical, H₂O₂ = hydrogen peroxide, NO = nitric oxide, MTA = mitochondria-targeted antioxidant. (b) Moreover, both physiological and non-physiological deviations in ROS levels could occur leading to oxidative eustress and oxidative distress, respectively. Oxidative distress causes lipid and protein oxidation, DNA damage, mitochondria damage and finally cellular death (figure created with Biorender.com accessed on 28 January 2024).

Figure 2

Clinical manifestations of OS and inflammation in four different neurodegenerative diseases (NDDs): Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS) (figure created with Biorender.com accessed on 28 January 2024).