Erkut BULDUK, Filiz YILDIRIM, Zuhal YILDIRIM

The possible role of Kallikrein-6, 7, and potassium channel proteins in Alzheimer’s disease

Objective: Although the formation mechanism of Alzheimer’s Disease (AD) is not known with certainty, two major proteins, beta amyloid of senile plaques and tau protein of neurofibrillary tangels are responsible for AD. One of the major factors in the development of the disease is the formation of in soluble amyloid deposits, and the other one is the increased tau phosphorylation. Kallikreins (KLK’s) are a sub-family of serine proteases that play a role in the etiology of AD which is characterized by neuronal damage and loss of function.Kallikrein (KLK)-6 and KLK-7 are known to be age-related protease and are found at high levels in the central nervous system (CNS). It was previously shown to be involved in proteolysis of extracellular proteins implicated in neurodegenerative diseases such as AD. In this study, we aimed to investigate the possible role of KLK-6 and KLK-7 in the pathogenesis of AD and the relationship between potassium channel proteins. Methods: A total of 35 Alzheimer’s patients over the age 65 years, followed-up by Polatlı Duatepe Government Hospital and 35 healthy individuals (control group) admitted to the neurology clinic for routine screening with cognitive status considered normal were included in this study. After a 12-hour hunger, KLK-6 and KLK-7 were measured with inwardly rectifying potassium channel protein (KCNJ3), and two-pore potassium channel protein (KCNK9) levels were measured by the Enzyme-Linked Immuno Sorbent Assay (ELISA) in the serum of the blood samples which were taken from the antecubital vein after centrifuging for 10 minutes at 2500xg. The differences between the two groups were tested by T- test. A value of p0.05). According to our findings, serum KLK- 6 and KLK-7 levels of Alzheimer’s group were significantly increased (p0.05). Conclusion: It is thought that the failure in preventing the abnormal protein folding and accumulation leads to AD in the brain. According to the findings of the present study, a positive correlation was detected between the levels of KLK-6 and KLK-7 and AD’s pathology.

Alzheimer hastalığında Kallikrein-6, 7 ve potasyum kanal proteinlerinin olası rolü

Amaç: Alzheimer hastalığının (AH) oluşum mekanizması kesin olarak bilinmemekle birlikte AH’dan sorumlu başlıca iki protein, senile plakların yapısındaki beta amiloid ve nörofibriler yumakların yapısındaki tau proteinidir. Hastalığa yol açan en önemli etmenlerden biri çözünür olmayan amiloid çökeltilerin oluşumu, diğeri ise artmış tau fosforillenmesidir. Kallikreinler, nöronal hasar ve işlev kaybı ile belirgin AH’nın etiyolojisinde rol oynayan, serin proteazların bir alt familyasıdır. Kallikrein (KLK)-6 ve KLK-7’nin merkezi sinir sisteminde (MSS) yüksek seviyelerde bulunan yaşa bağlı proteaz olduğu bilinmektedir. Daha once AH’ı gibi nörodejeneratif hastalıklarda yer alan hücre dışı proteinlerin proteolizine karıştığı gösterilmiştir. Bu çalışmada KLK-6 ve KLK-7’nin AH patogenezindeki olası rolünü ve potasyum kanal proteinleri arasındaki ilişkiyi araştırmayı amaçladık. Yöntem: Çalışmaya Polatlı Duatepe Devlet Hastanesinde takip edilen yaşları 65’in üzerinde olan 35 AH ve rutin tarama amacıyla nöroloji polikliniğine başvuran kognitif durumu normal olarak değerlendirilen 35 sağlıklı birey (control grubu) dahil edildi. 12 saat açlığı takiben antekübital venden alınan kan örnekleri 4°C’de 2500xg’de 10 dakika santrifüj edilerek, serum örneklerinde KLK-6 ve KLK-7 ile içeri doğru düzeltici potasyum kanalı (KCNJ3) ve iki gözenekli potasyum kanalı (KCNK9) protein düzeyleri enzim-bağımlı immunosorbent assay (ELISA) ile ölçüldü. Gruplar arasındaki fark T-test ile incelendi. p0.05). Alzheimer grubu control grubu ile karşılaştırıldığında serum KLK-6 ve KLK-7 düzeyleri anlamlı olarak artarken (p0.05). Sonuç: Beyinde anormal protein katlanmasının ve birikmesinin önüne geçilememesinin AH’ye yol açtığı düşünülmektedir. Bu araştırmanın bulgularına göre KLK- 6 ve KLK-7 düzeyleri ile AH’nın patolojisi arasında bir ilişki saptandı.

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