Impact of Nuclear Envelope Stress on Physiological and Pathological Processes in Central Nervous System

The nuclear envelope (NE) separates genomic DNA from the cytoplasm and provides the molecular platforms for nucleocytoplasmic transport, higher-order chromatin organization, and physical links between the nucleus and cytoskeleton. Recent studies have shown that the NE is often damaged by various stresses termed "NE stress", leading to critical cellular dysfunction. Accumulating evidence has revealed the crucial roles of NE stress in the pathology of a broad spectrum of diseases. In the central nervous system (CNS), NE dysfunction impairs neural development and is associated with several neurological disorders, such as Alzheimer's disease and autosomal dominant leukodystrophy. In this review, the structure and functions of the NE are summarized, and the concepts of NE stress and NE stress responses are introduced. Additionally, the significant roles of the NE in the development of CNS and the mechanistic connections between NE stress and neurological disorders are described.