AI Article Synopsis
- ALS is a progressive disease that results in the loss of motor neurons, leading to muscle paralysis and eventually death.
- Early signs of the disease often include increased cortical activity, which is linked to complex cellular changes.
- Ongoing research focuses on understanding the role of glutamate and inhibitory neurons in this hyper-excitability, which could help develop new treatments to protect motor neurons and improve patient outcomes.
Article Abstract
Amyotrophic lateral sclerosis (ALS) is a progressive neuromotor disease characterized by the loss of upper and lower motor neurons (MNs), resulting in muscle paralysis and death. Early cortical hyper-excitability is a common pathological process observed clinically and in animal disease models. Although the mechanisms that underlie cortical hyper-excitability are not completely understood, the molecular and cellular mechanisms that cause enhanced neuronal intrinsic excitability and changes in excitatory and inhibitory synaptic activity are starting to emerge. Here, we review the evidence for an anterograde glutamatergic excitotoxic process, leading to cortical hyper-excitability via intrinsic cellular and synaptic mechanisms and for the role of interneurons in establishing disinhibition in clinical and experimental settings. Understanding the mechanisms that lead to these complex pathological processes will likely produce key insights towards developing novel therapeutic strategies to rescue upper MNs, thus alleviating the impact of this fatal disease.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8145013 | PMC |
| http://dx.doi.org/10.3390/brainsci11050549 | DOI Listing |
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