Neurovascular Inflammaging in Health and Disease

Abstract

Aging is characterized by a chronic low-grade sterile inflammation dubbed as inflammaging, which in part originates from accumulating cellular debris. These, acting as danger signals with many intrinsic factors such as cytokines, are sensed by a network of pattern recognition receptors and other cognate receptors, leading to the activation of inflammasomes. Due to the inflammasome activity-dependent increase in the levels of pro-inflammatory interleukins (IL-1β, IL-18), inflammation is initiated, resulting in tissue injury in various organs, the brain and the spinal cord included. Similarly, in age-related diseases of the central nervous system (CNS), inflammasome activation is a prominent moment, in which cells of the neurovascular unit occupy a significant position. In this review, we discuss the inflammatory changes in normal aging and summarize the current knowledge on the role of inflammasomes and contributing mechanisms in common CNS diseases, namely Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and stroke, all of which occur more frequently with aging.

Keywords: aging; inflammaging; inflammasome; neurodegeneration; neuroinflammation; neurovascular unit; stroke.

Figure 1

Inflammasome activation by various age-related DAMPs and cytokines. ALR: absent in melanoma 2-like receptor, ASC: apoptosis-associated speck-like protein containing a caspase recruitment domain, ATP: adenosine triphosphate, gDNA/mtDNA: genomic/mitochondrial deoxyribonucleic acid, HMGB1: high mobility group box-1, IL: interleukin, IL1R: interleukin-1 receptor, MyD88: Myeloid differentiation primary response 88, NF-κB: nuclear factor kappa-light-chain-enhancer of activated B cells, NLR: nucleotide-binding oligomerization domain-like receptor, ROS: reactive oxygen species, SOD1: superoxide dismutase 1, TDP43: TAR DNA-binding protein 43, TLR: Toll-like receptor, TNF(R): tumor necrosis factor (receptor).

Figure 2

Pro-inflammatory shift in pathological aging. Aβ: amyloid-β, AD: Alzheimer’s disease, ALS: amyotrophic lateral sclerosis, ATP: adenosine triphosphate, PD: Parkinson’s disease, ROS: reactive oxygen species.