The role of neuroinflammation in neurodegenerative diseases: current understanding and future therapeutic targets

Abstract

Neuroinflammation refers to a highly complicated reaction of the central nervous system (CNS) to certain stimuli such as trauma, infection, and neurodegenerative diseases. This is a cellular immune response whereby glial cells are activated, inflammatory mediators are liberated and reactive oxygen and nitrogen species are synthesized. Neuroinflammation is a key process that helps protect the brain from pathogens, but inappropriate, or protracted inflammation yields pathological states such as Parkinson's disease, Alzheimer's, Multiple Sclerosis, and other neurodegenerative disorders that showcase various pathways of neurodegeneration distributed in various parts of the CNS. This review reveals the major neuroinflammatory signaling pathways associated with neurodegeneration. Additionally, it explores promising therapeutic avenues, such as stem cell therapy, genetic intervention, and nanoparticles, aiming to regulate neuroinflammation and potentially impede or decelerate the advancement of these conditions. A comprehensive understanding of the intricate connection between neuroinflammation and these diseases is pivotal for the development of future treatment strategies that can alleviate the burden imposed by these devastating disorders.

Keywords: Alzheimer’s disease; Parkinson’s disease; central nervous system; neurodegenerative disease; neuroinflammation.

FIGURE 1

It summarizes how neuroinflammation unfolds via the activation of microglia, astrocytes, and peripheral immune cells in neurological disorders. It visualizes the complex interplay between these cells, illustrating their roles in releasing inflammatory signals, causing a cascade of inflammatory responses, and collectively affecting neuronal health. It highlights the intricate network of interactions driving neuroinflammation, offering insight into the mechanisms underlying disease progression and potential targets for therapeutic intervention (Paul et al., 2021).

FIGURE 2

The inflammatory signaling pathway involved in AD is depicted in the figure. It involves the activation of microglia and astrocytes, leading to the release of inflammatory cytokines. This activation also triggers the release of amyloid beta, a protein that is crucial for the formation of neurofibrillary tangles. These tangles and proinflammatory cytokines contribute to neuronal dysfunction, a key characteristic of AD (Gómez-Benito et al., 2020; Pajares et al., 2020).

FIGURE 3

The intricate relationship between the gut and brain axes in PD is delineated by the schematic signaling pathway, with a focus on the inflammatory cascade triggered by dysbiosis at the gut lumen and BBB. Dysbiosis leads to an imbalance in gut microbiota composition, which in turn fosters the release of inflammatory cytokines. These cytokines breach the BBB and infiltrate the brain, where they exert their detrimental effects on dopaminergic neurons. The figure highlights the crucial role of dysbiosis-induced inflammation in contributing to the neurodegenerative characteristic of PD, emphasizing the potential therapeutic targets within the gut-brain axis for mitigating disease progression (Stefanis, 2012; Mey et al., 2023).

FIGURE 4

An illustrated summary of the brain regions impacted by major neurodegenerative disorders (Zahid et al., 2019).

FIGURE 5

Schematic summary of the neuroprotective potentials of stem cell therapies on neurological disorders (Deming et al., 2018).