Cortical projection neurons as a therapeutic target in multiple sclerosis

Area of Science:

• Neuroscience
• Immunology
• Genetics

Background:

• Multiple sclerosis (MS) is a chronic central nervous system disease affecting gray and white matter.
• Cortical lesions are increasingly recognized as critical drivers of irreversible disability in MS.
• Transcriptomic studies reveal cell type-specific alterations in cortical neurons, particularly excitatory projection neuron subtypes.

Purpose of the Study:

• To review the cortical mapping and molecular characteristics of excitatory projection neurons in MS.
• To highlight subtype-specific transcriptomic changes and vulnerability in MS cortical pathology.
• To discuss advanced MRI techniques for monitoring MS cortical pathology and therapeutic responses.

Main Methods:

• Literature review of PubMed articles (2000-2020).
• Analysis of transcriptomic data related to cortical neurons in MS.
• Review of magnetic resonance imaging (MRI) techniques for cortical lesion assessment.

Main Results:

• Excitatory projection neurons exhibit subtype-specific vulnerabilities in MS cortical lesions.
• Transcriptomic alterations provide insights into the molecular pathology of these neurons.
• Advanced MRI techniques show promise for tracking disease progression and treatment efficacy.

Conclusions:

• Excitatory cortical projection neurons represent a significant therapeutic target for progressive MS.
• Detailed understanding of neuron subtype pathology and spatial mapping is crucial for developing targeted therapies and biomarkers.
• Novel therapeutic strategies are needed to protect vulnerable excitatory cortical projection neurons in MS.