Molecular Biomarkers for Amyotrophic Lateral Sclerosis

Chi-Shin      Hwang; Chia-Hung      Hsieh; Guan-Ting      Liu; Si-Yi      Chen; Johnannes      Scheng-Ming Tschen; Hao-Teng      Chang

Abstract

Amyotrophic lateral sclerosis (ALS) is a complicated and devastating neurodegenerative disease. To date, its diagnosis is still mainly based on clinical symptoms and electromyographic findings. High rates of misdiagnosis and delayed diagnosis are the major hurdles in ALS treatment. Thus, searching for biomarkers to improve clinical diagnosis of ALS is a highly desirable goal. Here we review current potential biomarkers derived from the various pathogenic mechanisms of ALS, including those involved in oxidative stress, synaptic excitotoxicity, neuroinflammation and the autoimmune response. Oxidative stress results from genetic mutation or an increase in protein aggregation, synaptic excitotoxicity arising from elevated levels of glutamate and D-serine, and the neuroinflammation occurring from elevated levels of inflammatory molecules and cytokine receptors. Some of these biomarkers could be used for monitoring the disease progression and to assess effectiveness of treatment for ALS. We conclude that neuroinflammation plays a crucial role in ALS, which may lead to a better understanding of this devastating disease and ultimately to a cure. In addition, the identification of new biomarkers would undoubtedly provide critical insights into the pathogenesis of ALS.

Keywords: Amyotrophic lateral sclerosis, biomarker, pathogenesis and autoantibody, oxidative stress, synaptic excitotoxicity, neuroinflammation, protein aggregation, glutamate and D-serine, Cu/Zn superoxide dismutase, heat shock proteins