Major advances in amyotrophic lateral sclerosis in 2020

摘要

Amyotrophic lateral sclerosis (ALS), a heterogeneous syndrome recognised clinically as a progressive degeneration of the upper and lower motor neurons, is traditionally classed as a neuromuscular disorder. However, major advances in cell and molecular biology, neuroimaging, neuroelectric signal analyses, and neuropathology have categorically shown that ALS should be considered to be a neurodegenerative disorder, albeit with a substantial neuromuscular component.1 Although the biological processes underlying the pathogenesis and progression of the disease are multifactorial, there is increasing evidence that ALS is characterised by early cortical hyperexcitability with altered synaptic integrity, possibly mediated by the deposition of TAR DNA-binding protein 43 (TDP-43),2 followed by more widespread disruption of neuronal networks.3