Nörodejeneratif Hastalıklarda Umut Verici Bir Terapötik Hedef: Sestrin-2

Alzheimer, Parkinson, Huntington ve amyotrofik lateral skleroz dâhil olmak üzere nörodejeneratif hastalıklar günümüz dünyasında giderek daha yaygın hale gelen, multifaktöriyel ve ilerleyici tipte hastalıklardır. Nörodejeneratif bozuklukların yaygın etiyolojilerinin başında yaşlanma, oksidatif stres ve mitokondriyal disfonksiyon gelmektedir. Nörodejeneratif hastalıkların tedavisinde kullanılan güncel ilaçlar hastanın yaşam kalitesini iyileştirse de hastalığın gelişimini ve ilerlemesini yavaşlatan veya önleyen bir tedavi henüz mevcut değildir. Bu ilaçların en büyük dezavantajı ise kronik kullanımlarında ciddi yan etkilerle karşılaşılmasıdır. Bu kapsamda yeni terapötik hedeflere yönelik uzun vadede yan etki profili düşük yeni ajanlara ihtiyaç duyulmaktadır. Son zamanlarda gerçekleştirilen çalışmalarda, stresle indüklenebilir bir metabolik protein olan Sestrin-2’nin reaktif oksijen türlerini baskıladığı, metabolizma ve inflamasyonu düzenlediği ve genotoksisite ve oksidatif stres, mitokondriyal disfonksiyon, endoplazmik retikulum stresi ve hipoksi dâhil olmak üzere çeşitli zararlı uyaranlara karşı hücresel koruma sağladığı gösterilmiştir. Sestrin-2’nin düzenlenmesi ve sinyal mekanizmalarına ilişkin çığır açan araştırmalarla, potansiyel rolü ve konak yanıtındaki önemi konusundaki bilgilerimiz önemli derecede artmış olsa da Sestrin-2’nin nörodejeneratif hastalıklarda işlevleri için daha fazla çalışmaya ihtiyaç duyulmaktadır. Bu çalışmada, nörodejeneratif hastalıklarda önemli bir terapötik hedef olma potansiyeline sahip Sestrin-2’ye dikkat çekmek amacıyla literatürdeki bilgiler detaylı bir şekilde derlenmiştir.

Anahtar Kelimeler:

Nörodejeneratif Hastalıklar, Oksidatif Stres, Alzheimer Hastalığı

A Promising Therapeutic Target in Neurodegenerative Diseases: Sestrin-2

Neurodegenerative diseases such as Alzheimer’s, Parkinson’s, Huntington’s, and amyotrophic lateral sclerosis are the more common, multi-factorial, and progressive diseases in today’s world. The most common etiology of neurodegenerative disorders is aging, oxidative stress, and mitochondrial dysfunction. Modern medicines for the treatment of neurodegenerative diseases improve the patient’s quality of life, but no treatment slows down or prevents the development and progression of the disease. The greatest disadvantage of these drugs is that they cause serious side effects in their chronic use. New agents with low side effect profiles in the long term are needed for new therapeutic targets. Recent studies have shown that Sestrin-2, a stress-inducible metabolic protein, suppresses reactive oxygen species, regulates metabolism and inflammation, and provides cellular protection against various harmful stimuli including genotoxicity and oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress, and hypoxia. With groundbreaking research into the regulation and signaling mechanisms of sestrin-2, although our knowledge of its potential role and its importance to host response has increased considerably, its function in neurodegenerative diseases remains unclear. The present study compiled in detail the information in the literature to draw attention to sestrin-2, which has the potential to be a major therapeutic target in neurodegenerative diseases.

Keywords:

Neurodegenerative Diseases, Oxidative Stress, Alzheimer's disease,

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