Neuroinflammation: A Potential Risk for Dementia

Abstract

Dementia is a neurodegenerative condition that is considered a major factor contributing to cognitive decline that reduces independent function. Pathophysiological pathways are not well defined for neurodegenerative diseases such as dementia; however, published evidence has shown the role of numerous inflammatory processes in the brain contributing toward their pathology. Microglia of the central nervous system (CNS) are the principal components of the brain's immune defence system and can detect harmful or external pathogens. When stimulated, the cells trigger neuroinflammatory responses by releasing proinflammatory chemokines, cytokines, reactive oxygen species, and nitrogen species in order to preserve the cell's microenvironment. These proinflammatory markers include cytokines such as IL-1, IL-6, and TNFα chemokines such as CCR3 and CCL2 and CCR5. Microglial cells may produce a prolonged inflammatory response that, in some circumstances, is indicated in the promotion of neurodegenerative diseases. The present review is focused on the involvement of microglial cell activation throughout neurodegenerative conditions and the link between neuroinflammatory processes and dementia.

Keywords: Alzheimer’s disease; chemokines; cytokines; dementia; microglial cell activation; neuroinflammation; phagocytosis.

Figure 1

Role of neuroinflammation and dementia. The presence of coexisting neurological disorders such as Alzheimer’s disease, Parkinson’s disease, and exposure to neurotoxic stimulus causes increased chemokines and NLRP3 activation that eventually leads to neuroinflammation. Moreover, neurotoxic stimulus also induces neuroinflammation via modulation of MAPKs, Akt/PI3K, mTOR, ER stress and mitochondrial dysfunction. Additionally, these neurological disorders cause a dysfunctional release of neurotransmitters that further interferes with the function of CREB, BDNF, LTP, etc., and causes dementia.

Figure 2

Showing mediators and neuroinflammatory modulators and dementia. Coexisting neurological disorders such as Alzheimer’s disease, Parkinson’s disease and exposure to neurotoxic stimulus cause damage to BBB via alteration in endothelial cells and tight junctions. Damaged BBB causes NLRP3, TLR-4 and microglial activation, macrophage infiltration and nuclear translocation of NF-kB that cumulatively causes oxidative stress and neuroinflammation that leads to dementia.

Figure 3

Showing graphical abstract.