The involvement of Akt and GSK-3: Two pathways, two pathology

Yıl 2014, Cilt: 4 Sayı: 1, 51 - 57, 25.04.2014

Ceren Şahin Gökhan Ünal Feyza Arıcıoğlu

Öz

Today a growing body of evidence has directed much attention to the hyperactivation of glycogen synthase kinase-3 (GSK-3) in several psychiatric disorders including schizophrenia and mood disorders. Regulatory mechanisms of GSK-3 activation have become important issues since GSK-3, a member of serine/threonine kinase family, is identified to have numerous roles in intracellular functions by its effect on regulation of at least fifty protein substrates. Among these, particularly the inhibitory control of GSK-3 by Akt is considered as one of the most intriguing mechanisms in psychiatric manner. Hence, in schizophrenia and depression, disruption of Akt-mediated regulation of GSK-3 via two distinct pathways is resulted in hyperactivated GSK-3. In the present study, alterations of two Akt-mediated regulatory mechanisms of GSK-3; phosphoinositide-3 kinase (PI3K) and ß-arrestin complex mediated pathways are reviewed in depression and schizophrenia respectively, and how these alterations reflect GSK-3 activity and consequently contribute to the development of these conditions. Finally the importance of regulatory mechanisms on GSK-3 is highlighted through the aspect of Akt-GSK-3 engagement by possibly bringing novel aspects to the treatments of these disorders.

Key words: Akt, GSK-3, PI3K, ß-arrestin, depression, schizophrenia

Anahtar Kelimeler

Akt, GSK-3, PI3K, β-arrestin, depression, schizophrenia

Akt-GSK-3 ilişkisi: İki ayrı yolak iki ayrı hastalık

Öz

Günümüzde şizofreni ve duygu durum bozukluklarını kapsayan birçok psikiyatrik hastalıkta glikojen sentaz kinaz-3 (GSK-3) hiperaktivitesine işaret edilmektedir. Serin / treonin kinaz ailesinin bir üyesi olan GSK-3’ün ellinin üzerinde proteinin regülasyonunda rol alarak hücre içi fonksiyonlarda yaygın görevlerinin olması, GSK-3 aktivitesi üzerine etkili hücre içi düzenleyici mekanizmaların önemini gündeme getirmiştir. İlgili mekanizmalardan özellikle Akt’ın GSK-3 aktivitesi üzerindeki inhibe edici rolü, psikiyatrik hastalıklar açısından oldukça dikkat çekici bir mekanizma olarak karşımıza çıkmaktadır. Nitekim Akt’ın iki farklı yolak üzerinden GSK-3 aktivitesini düzenlemesi, depresyon ve şizofreni tablosunda bozulan Akt aktivitesi sonucu GSK-3 hiperaktivitesine neden olmaktadır. Burada GSK-3 aktivitesinin düzenlenmesinde rol oynayan fosfoinozitid-3 kinaz (PI3K) ve ß-arrestin kompleksi üzerinden işleyen Akt aracılı iki farklı yolağın sırasıyla depresyon ve şizforeni tablolarında gösterdikleri değişim ile bu değişimin GSK-3 aktivitesine olan yansımasına değinilerek, Akt-GSK-3 ilişkisi bakış açısıyla GSK-3 aktivitesi üzerindeki düzenleyici mekanizmaların bu hastalıkların tedavisine getirebileceği olası boyutların önemine dikkat çekilmesi amaçlanmıştır.

Anahtar Kelimeler : Akt, GSK-3, PI3K, ß-arrestin, depresyon, şizofreni

Anahtar Kelimeler

Akt, GSK-3, PI3K, β-arrestin, depresyon, şizofreni

Kaynakça

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