Chenzhao He1  · Debao Wu1  · Ailian Du1  · Liang Zhang1,2

1 Department of Neurology, Shanghai Key Laboratory of Emotions and Affective Disorders, Songjiang Research Institute, Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China 

2 Institute of Neuroscience, Key Laboratory of Molecular Neurobiology, Ministry of Education, Navy Military Medical University, Shanghai 200433, China

Abstract

White matter, constituting nearly half of the human brain, is increasingly recognized as a dynamic regulator of neural communication, metabolism, and cognition rather than a passive conduit for signal transmission. Recent advances in neuroimaging, molecular biology, and single-cell transcriptomics have revealed that myelin and oligodendrocytes play essential roles in neural plasticity and disease. Here, we synthesize current understanding of white matter organization and myelin function, emphasizing its contributions to conduction efficiency, metabolic support, and network optimization. We further discuss mechanisms of myelin plasticity and highlight its role in learning, adaptation, and repair. Integrating evidence across developmental, immune-mediated, neurodegenerative, and psychiatric disorders, we propose that white matter pathology constitutes a primary driver of brain dysfunction. Finally, we summarize emerging regenerative strategies—including cell and gene therapies, OPC-targeted interventions, and neuromodulation—highlighting translational opportunities for restoring myelin integrity and circuit function. This review reframes white matter as a promising therapeutic frontier.

Keywords

White matter plasticity; Oligodendrocytes; Myelin pathology; Regenerative therapy

[SpringerLink]