Mikroglial Toll-benzeri Reseptörlerin Alzheimer ve Parkinson Hastalıklarındaki Rolü

Öz

Patern tanıma reseptörleri içinde en iyi tanımlanmış olan Toll-benzeri reseptörler, santral sinir sisteminde ?makrofaj benzeri? fonksiyona sahip mikroglia hücrelerinde bulunurlar. Amiloid-beta proteini ve agrege ?-sinüklein gibi hasarla ilişkili moleküler motifleri tanıyan Toll-benzeri reseptörler, mikroglia hücrelerinin proinflamatuar fenotipe kaymasına neden olarak ve tümör nekroz faktör-alfa (TNF-?), interlökin (IL)-1, IL-6, IL-12 gibi proinflamatuar mediyatörler aracılığıyla inflamasyonu tetikler. Nörodejeneratif hastalıklarda mikroglial Toll-benzeri reseptör aracılı sinyalizasyonun önemli bir role sahip olduğu gösterildiği için Alzheimer ve Parkinson hastalıklarında (i) aşılar, (ii) küçük moleküllü inhibitörler, (iii) var olan ilaçların yeni bir endikasyon için kullanılması ve (iv) doğal bileşikler gibi Toll-benzeri reseptörleri hedef alan yeni tedavi yaklaşımları bulunmaktadır. Preklinik çalışmalarda başarılı sonuçlar göstermiş olan ilaç adaylarının birçoğu klinik fazlarda aynı başarıyı yakalayamamıştır. Buna rağmen, Toll-benzeri reseptörler ve sinyal yolakları üzerinde etkili moleküllerle ilgili çalışmaların sayısı artmaya devam etmektedir.

Anahtar Kelimeler

• Mikroglia
• Toll-benzeri reseptörler
• Alzheimer hastalığı
• Parkinson hastalığı

The Role of Microglial Toll-like Receptors in Alzheimer?s and Parkinson?s Disease

Abstract

Toll-like receptors, the best defined among the different pattern recognition receptors, are found on microglia cells that have a "macrophage-like" function in the central nervous system. Toll-like receptors that recognize damage-related molecular motifs such as amyloid-beta protein and aggregated ?-synuclein, trigger inflammation via switching the microglial phenotype to proinflammatory side and releasing proinflammatory mediators such as tumor necrosis factor-alpha (TNF-?), interleukin (IL)-1, IL-6, IL-12. Since Toll-like receptor-mediated signaling has been shown to play an important role in neurodegenerative diseases, there are new treatment approaches targeting Toll-like receptors including (i) vaccines, (ii) small molecule inhibitors, (iii) use of existing drugs for a new indication and (iv) use of natural compounds. Although many compounds have shown promising results in preclinical studies, they have not achieved the same success in clinical trials. However, the studies with compounds targeting Toll-like receptors and signaling cascades are continuing to increase.

Keywords

• Microglia
• Toll-like receptors
• Alzheimer?s disease
• Parkinson?s disease

Kaynakça

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