Current Trends in Neurodegeneration: Cross Talks between Oxidative Stress, Cell Death, and Inflammation

Abstract

The human body is highly complex and comprises a variety of living cells and extracellular material, which forms tissues, organs, and organ systems. Human cells tend to turn over readily to maintain homeostasis in tissues. However, postmitotic nerve cells exceptionally have an ability to regenerate and be sustained for the entire life of an individual, to safeguard the physiological functioning of the central nervous system. For efficient functioning of the CNS, neuronal death is essential, but extreme loss of neurons diminishes the functioning of the nervous system and leads to the onset of neurodegenerative diseases. Neurodegenerative diseases range from acute to chronic severe life-altering conditions like Parkinson's disease and Alzheimer's disease. Millions of individuals worldwide are suffering from neurodegenerative disorders with little or negligible treatment available, thereby leading to a decline in their quality of life. Neuropathological studies have identified a series of factors that explain the etiology of neuronal degradation and its progression in neurodegenerative disease. The onset of neurological diseases depends on a combination of factors that causes a disruption of neurons, such as environmental, biological, physiological, and genetic factors. The current review highlights some of the major pathological factors responsible for neuronal degradation, such as oxidative stress, cell death, and neuroinflammation. All these factors have been described in detail to enhance the understanding of their mechanisms and target them for disease management.

Keywords: apoptosis; cell death; necrosis; neurodegeneration; neuroinflammation; oxidative stress.

Figure 1

Some of the common factors responsible for the initiation/progression of neurological diseases.

Figure 2

The factors that are involved in the pathways of cell death. Legend: JNK—c-Jun amino-terminal kinase; DLK—dual leucine zipper kinase.

Figure 3

The factors that cause oxidative stress and the physiological changes that come as a result of increased reactive oxygen species.

Figure 4

Synthesizing the process of oxidative stress-mediated neurodegeneration. Legend: ROS—reactive oxygen species; RNS—reactive nitrogen species; UV—ultraviolet; NADP—nicotinamide adenine dinucleotide.

Figure 5

Environmental factors, toxins, chemicals, or genetic factors that can lead to the activation of anti-myelin T-lymphocytes. Legend: IL—interleukin; IP—inducible protein.