Abstract
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with the progressive loss of motor neurons, leading to a fatal paralysis. According to whether there is a family history of ALS, ALS can be roughly divided into two types: familial and sporadic. Despite decades of research, the pathogenesis of ALS is still unelucidated. To this end, we review the recent progress of ALS pathogenesis, biomarkers, and treatment strategies, mainly discuss the roles of immune disorders, redox imbalance, autophagy dysfunction, and disordered iron homeostasis in the pathogenesis of ALS, and introduce the effects of RNA binding proteins, ALS-related genes, and non-coding RNA as biomarkers on ALS. In addition, we also mention other ALS biomarkers such as serum uric acid (UA), cardiolipin (CL), chitotriosidase (CHIT1), and neurofilament light chain (NFL). Finally, we discuss the drug therapy, gene therapy, immunotherapy, and stem cell-exosomal therapy for ALS, attempting to find new therapeutic targets and strategies. A challenge is to study the various mechanisms of ALS as a syndrome. Biomarkers that have been widely explored are indispensable for the diagnosis, treatment, and prevention of ALS. Moreover, the development of new genes and targets is an urgent task in this field.
Highlights
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease in adults that was first described by a neurobiologist Jean-Martin Charcot in the 1870s and was originally called Charcot’s triad
An RNA analysis on Fused in sarcoma (FUS) mutations in motor neurons from induced pluripotent stem cells in ALS indicates that abnormal gene expression and splicing changes are related to FUS mutations [66,67]. This suggests that the abnormal phase transition and RNA metabolism of FUS protein may be involved in the pathogenesis of ALS
Studies have found that from the aspect of mitochondrial dynamics, the dysfunction mediated by mutant SOD1G93A in ALS is related to enhanced apoptosis in osteocytes, which may be a potential mechanism of bone loss during the progression of ALS [104]
Summary
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease in adults that was first described by a neurobiologist Jean-Martin Charcot in the 1870s and was originally called Charcot’s triad. There is an urgent need to develop a treatment plan, to slow the progression of the disease, and to cope with the of its pathogenesis, promoting the development of early and specific diagnostic methods. There is an urgent need to develop a treatment plan, to slow the progression of the have conducted a lot of related studies, but the pathogenesis of ALS is still disease, and to cope with the secondary consequences of malnutrition and respiratory unclear. The latest discovery of the underlying mechanism of ALS will help reduce biomarkers and treatment strategies in recent years, and have a systematic understanding the incidence of ALS, slow down the progression of the disease, and find new targets for of ALS. Incidence of ALS, slow down the progression of the disease, and find new targets for the treatment of ALS
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