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Journal of Neurology and Neurorehabilitation Research
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Volume 3
Page 50
allied
academies
J u n e 2 8 - 2 9 , 2 0 1 8 | D u b l i n , I r e l a n d
Joint Event on
NEUROSCIENCE AND NEUROLOGICAL DISORDERS
PSYCHIATRY AND PSYCHOLOGICAL DISORDERS
&
International Conference on
International Conference on
MECHANISMS OF SELF-MAINTENANCE OF CHRONIC
INFLAMMATION IN ALZHEIMER’S DISEASE
Jerzy Leszek
Wroclaw Medical University, Poland
L
ow grade inflammatory reactions are considered important factors that accelerate the progression of Alzheimer’s disease. Major
receptors of innate immunity, Toll-like receptors (TLRs) and receptor for advanced glycation end-product (RAGE), play a central
role in triggering and driving these chronic inflammatory reactions. Signal transduction pathways from TLR and RAGE receptors
lead to activation of transcription factors, mainly NF-kB and AP-1, which enhance the synthesis of proinflammatory cytokines.
Activation of NF-kB enhances the transcription and expression of additional amounts of RAGE receptor protein in immune cell
membranes, which results in increased further activation of this receptor. Many of the RAGE signal transduction pathway proteins
can activate proteins from TLR pathways and vice versa. Such RAGE-TLR cross-activation emerges as an important driving force
for maintenance of chronic inflammation in Alzheimer’s disease, which finally increases the amount of proinflammatory cytokines
released. Intractable, self-sustaining inflammatory reactions in the brain tissue, accompanied by an increased level of released
proinflammatory cytokines, create a microenvironment for the development of an autoimmune component in neurodegeneration.
Lowering the level of RAGE activation should weaken the RAGE-TLR cooperation and could bring about a significant slowdown in
the disease progression.
jerzy.leszek@umed.wroc.plJ Neurol Neurorehabil Res 2018, Volume 3