Κατεύθυνση Κλινική ΝευροφυσιολογίαLibrary of the School of Health Sciences
Βουμβουράκης Κωνσταντίνος-Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ, Επιβλέπων
Τσιβγούλης Γεώργιος-Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Μπονάκης Αναστάσιος-Επίκουρος Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Ανοσολογικές προσεγγίσεις σε φλεγμονή και εκφύλιση στο Κεντρικό Νευρικό Σύστημα
The immunology of inflammation and degeneration in Central Nervous System
The immune system plays an important role in the regulation of the neuroinflammation, as it provides protection against pathogens and also promotes tissue repair. On the other hand, chronic low-grade inflammation can be detrimental and may be a common pathogenic feature among severe Central Nervous System (CNS) diseases.
Chronic inflammation is induced by diverse molecular and cellular mechanisms.Autoimmune/inflammatory CNS diseases are characterized by T-cell infiltration, increased production of (auto)antibodies, presence of activated CD4+ Tcells, as well as T-memory cells and B-cells.
In neurodegeneration, microglial cells are the prominent cellular component in immune response. Toll-like receptors (TLRs) and damage-associated molecular patterns(DAMPs) recognize protein aggregates and promote cellular activation of microglial cells. These cells adopt either a neurotoxic or a neuroprotective phenotype. The latter process depends on the CNS microenvironment and is regulated by molecular intracellular interactions between cytokines, complement, and blood-brain barrier elements.
Inflammatory and degenerative processes are present in severe CNS diseases, such as Alzheimer's disease, Parkinson's disease, Amyatrophic Lateral Sclerosisand Multiple Sclerosis. The induction of the inflammatory/degenerative process is unique for each disease entity. Nevertheless, there is significant overlap in the propagation of the inflammatory/degenerative cascades,as far as detection, transmittion, regulation and production of neurotoxic mediators are concerned.
The common denominator between inflammatory/autoimmune and degenerative diseases is the combination of highcellular energy demands along withdeficient cellularenergy production. These processes promote axonal loss and apoptosis in the long run.
Inflammation and degeneration may coexist in the same CNS disease. The mechanisms,by which one of these two different processes prevails over the other, are still not fully understood.
In this review article we attempt to analytically describetheinflammatory and degenerative mechanismswhich underpin the pathogenesis of major CNS diseases, as defined by basic neuroimmunologyprinciples. The complete understanding of these processesis essential in the future research for the development of targeted therapies against such severe CNS diseases.
Main subject category:
Inflammation, Degeneration, Innate immunity, Adaptive immunity, Multiple sclerosis, Neurodegenerative disorders
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