Perineuronal nets: Role in normal brain physiology and aging, and pathology of various diseases

Perineuronal nets (PNNs) are a specialized extracellular matrix in the central nervous system. They are widely distributed in the brain, with distribution patterns varying by brain region. Their unique structure and composition allow them to play an important role in a range of physiological and pathological activities. In this article, we review the composition and structure of PNNs across different life stages, and provide a detailed analysis and comparison of the region-specific distribution patterns of PNNs in different brain areas. We also discuss the specific mechanisms by which PNNs are involved in plasticity, memory, and neuroprotection. Furthermore, we describe the abnormal changes in PNNs in aging and various brain diseases, such as Alzheimer's disease, Parkinson's disease, drug addiction, and schizophrenia. Finally, we review emerging and established therapeutic strategies targeting PNNs to modulate brain function and address neurological disorders from three perspectives: gene therapy, nanotechnology, and biomaterials. This review summarizes the physiological roles of PNNs at different stages of life and the mechanisms by which PNNs abnormalities contribute to various brain diseases, providing insights for potential therapeutic approaches.