Inflammation as common link to progressive neurological diseases

Abstract

Life expectancy has increased immensely over the past decades, bringing new challenges to the health systems as advanced age increases the predisposition for many diseases. One of those is the burden of neurologic disorders. While many hypotheses have been placed to explain aging mechanisms, it has been widely accepted that the increasing pro-inflammatory status with advanced age or “inflammaging” is a main determinant of biological aging. Furthermore, inflammaging is at the cornerstone of many age-related diseases and its involvement in neurologic disorders is an exciting hypothesis. Indeed, aging and neurologic disorders development in the elderly seem to share some basic pathways that fundamentally converge on inflammation. Peripheral inflammation significantly influences brain function and contributes to the development of neurological disorders, including Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis. Understanding the role of inflammation in the pathogenesis of progressive neurological diseases is of crucial importance for developing effective treatments and interventions that can slow down or prevent disease progression, therefore, decreasing its social and economic burden.

Kynurenic acid inflammatory signaling expands in primates and impairs prefrontal cortical cognition

“…Longstanding data from rodents, macaques and humans have shown increased KYNA levels in CNS with advanced age 31–33,85 , consistent with greater inflammation with age 9,86,87 . The current data are consonant with these findings, as aged macaques were more responsive to KAT-II inhibitors than younger adult macaques, and showed greater levels of plasma kynurenine.…”

Neuroinflammation and Neurodegenerative Diseases: How Much Do We Still Not Know?

“…Based on the evidence described above, mTOR and AKT pathways, as well as JAK-STAT, and PPARγ, and Notch pathways, constitute other crucial pathways in neuroinflammation [9,[110][111][112][113][114][115]. They represent highly conserved signaling hubs that coordinate neuronal activity and brain development and participate in neuroinflammation.…”