Amyotrofik Lateral Skleroz (ALS) Hastalığının Patogenezi

Öz

İlk olarak on dokuzuncu yüzyılda Charcot tarafından tanımlanan  Amyotrofik Lateral Skleroz (ALS), genellikle üç ile beş yıllık bir sağkalım ile seyreden, sürekli ilerleyici bir nörodejeneratif hastalıktır. Motor nöronlarda dejenerasyon ve ölüm ile karakterize olup,  kortikal motor hücreler(piramidal ve Betz hücreleri), kortikospinal trakt, ve ön boynuz hücrelerinde belirgin aksonal kayıp görülür. ALS’nin etiyolojisi tam olarak bilinmemekle birlikte, patogenezinde pek çok farklı etmenin rol oynadığı ileri sürülmektedir. Genetik, oksidatif stres, glutamat eksitoksisitesi, mitokondrial disfonksiyon, aksonal transport bozukluğu, nöroinflamasyon, RNA bozuklukları bunlardan başlıcalarıdır. Yine nörotrofik faktörler, organeller arası trafiğin bozulması, sinyal yolaklarında bozukluk, metabolik değişiklikler gibi faktörlerin de süreçte rol oynadığı düşünülmektedir. Bu derlemede ALS hastalığının patogenezi gözden geçirilmiştir.

Anahtar Kelimeler

• amyotrophic lateral sclerosis,pathogenesis,etiology,genetic,mitochondrial dysfunction

Pathogenesis of Amyotrophic Lateral Sclerosis (ALS)

Abstract

Amyotrophic Lateral Sclerosis (ALS), first described by Charcot in the nineteenth century, is a progressive neurodegenerative disease, usually with a three to five-year survival. ALS is characterized by degeneration and death in motor neurons. Cortical motor cells (pyramidal and Betz cells), corticospinal tract and anterior horn cells show prominent axonal loss. Although the etiology of ALS is not known exactly, it is suggested that many different factors play a role in its pathogenesis. Genetics, oxidative stress, glutamate excitotoxicity, mitochondrial dysfunction, axonal transport disorder, neuroinflammation, RNA disorders are the main ones. Factors such as neurotrophic factors, impaired intercellular traffic, disturbance of signaling pathways and metabolic changes are thought to play a role in the process. In this article, pathogenesis of ALS disease is reviewed.

Keywords

• amyotrophic lateral sclerosis,pathogenesis,etiology,genetic,mitochondrial dysfunction

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