The neuropathobiology of multiple sclerosis

Area of Science:

• Neuroscience
• Immunology
• Neurology

Background:

• Multiple sclerosis (MS) involves chronic inflammation and neuronal deregulation, leading to progressive disability.
• Current MS therapies primarily address acute relapses, leaving a gap in treating chronic disability progression.
• Understanding neuron-intrinsic factors influencing vulnerability to inflammation is crucial for developing new treatments.

Purpose of the Study:

• To provide a neuron-centric review of recent advances in understanding neuronal responses in MS pathology.
• To explore the inflammatory central nervous system (CNS) environment's neurotoxic mechanisms.
• To discuss therapeutic strategies targeting neuronal resilience and actuators for MS.

Main Methods:

• Review of current literature on neuronal responses in multiple sclerosis.
• Analysis of inflammatory CNS environment and its impact on neuronal function.
• Compilation of preclinical data on neuronal actuators for neurodegeneration.

Main Results:

• The inflammatory CNS environment induces neurotoxicity via ion imbalance, excitotoxicity, oxidative stress, and neuro-immune interactions.
• Neuronal damage involves mitochondrial dysfunction, epigenetic dysregulation, impaired transport, protein aggregation, and cell death pathways.
• Neuronal damage perpetuates CNS inflammation by activating glia and affecting neighboring neurons.

Conclusions:

• Targeting neuron-intrinsic factors and neuronal actuators presents a promising therapeutic avenue for multiple sclerosis.
• Several neuronal actuators have shown potential in preclinical studies and some are in clinical trials.
• Developing therapies that enhance neuronal resilience is key to halting chronic disability progression in MS.