Driven to decay: Excitability and synaptic abnormalities in amyotrophic lateral sclerosis

Area of Science:

• Neuroscience
• Neurology
• Genetics

Background:

• Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease.
• It is characterized by the progressive death of motor neurons, leading to muscle atrophy and eventual death.

Purpose of the Study:

• To review the common etiology of sporadic and familial ALS.
• To discuss the role of synaptic and intrinsic hyperexcitability in corticospinal motor neurons (CSMNs) and motor neurons (MNs).

Main Methods:

• Review of existing literature on ALS pathogenesis.
• Analysis of data from transgenic mouse models expressing ALS-associated mutations.
• Discussion of clinical and pathological findings in both familial and sporadic ALS cases.

Main Results:

• Cortical electrical abnormalities and glutamate-mediated alterations in CSMNs and MNs are implicated in ALS.
• Synaptic and intrinsic hyperexcitability of CSMNs and MNs, along with structural alterations, are central to ALS pathogenesis.
• Extramotor dysfunction is associated with neuronal structural and functional changes.

Conclusions:

• A common pathological pathway may underlie both familial and sporadic ALS.
• Hyperexcitability and structural changes in motor neurons are key features of ALS.
• Further research into the dying-forward and dying-back mechanisms is crucial for understanding ALS progression.