Inflammation and Anti-Inflammatory Strategies for Alzheimer’s Disease – A Mini-Review

Abstract

Until recently, the central nervous system (CNS) has been thought to be an immune privileged organ. However, it is now understood that neuroinflammation is linked with the development of several CNS diseases including late-onset Alzheimer’s disease (LOAD). The development of inflammation is a complex process involving a wide array of molecular interactions which in the CNS remains to be further characterized. The development of neuroinflammation may represent an important link between the early stages of LOAD and its pathological outcome. It is proposed that risks for LOAD, which include genetic, biological and environmental factors can each contribute to impairment of normal CNS regulation and function. The links between risk factors and the development of neuroinflammation are numerous and involve many complex interactions which contribute to vascular compromise, oxidative stress and ultimately neuroinflammation. Once this cascade of events is initiated, the process of neuroinflammation can become overactivated resulting in further cellular damage and loss of neuronal function. Additionally, neuroinflammation has been associated with the formation of amyloid plaques and neurofibrillary tangles, the pathological hallmarks of LOAD. Increased levels of inflammatory markers have been correlated with an advanced cognitive impairment. Based on this knowledge, new therapies aimed at limiting onset of neuroinflammation could arrest or even reverse the development of the disease.

Gx‐50 reduces β‐amyloid‐induced TNF‐α, IL‐1β, NO, and PGE2 expression and inhibits NF‐κB signaling in a mouse model of Alzheimer's disease

“…And, most importantly, under the pathologic condition with Aβ, gx-50 exhibited strong anti-inflammatory effects. Overall, the overactivated microglia, pro-inflammatory cytokines and sustained deposition of Aβ plaques result in a positive feedback loop of enduring and irreversible inflammation that ultimately contributes to the process of AD [26,42]. Based on these results and previous study of Aβ-oligomer disaggregation [9], gx-50 may involve in this feed-forward loop of inflammation and exert the anti-inflammatory effects in two manners (Fig.…”

Perispinal etanercept: a new therapeutic paradigm in neurology

“…[3,4,6,10,55,56,59, 62,70,73,80,82,84,85,107,169,170] • Spinal cord injury [7,143,144,[146][147][148][149][150] • Traumatic brain injury [136] • Stroke [137][138][139][140] …”

Low Grade Inflammation as a Common Pathogenetic Denominator in Age-Related Diseases: Novel Drug Targets for Anti-Ageing Strategies and Successful Ageing Achievement

“…A better understanding of the interplay between cytokines, their receptor activity, second messengers, lipid metabolism and protein modification is necessary. Although there are many events which can lead to neuroinflammation, this process represents a common pathway of disease development [41].…”