The emerging role of chitinase-3-like-1 protein in neurodegeneration

Neurodegenerative diseases (NDDs) are characterised by the progressive degeneration of neurons in the brain, resulting in impairments in memory, cognition, and motor abilities. Common pathological features include altered energy metabolism, neuroinflammation, death of neurons, aberrant protein aggregation, and synaptic dysfunction. Chitinase-3-like-1 (CHI3-L1) is an evolutionarily conserved protein involved in variety of biological processes such as neuroinflammation, tissue remodelling and angiogenesis. Elevated levels of CHI3-L1 have been detected in the cerebrospinal fluid and plasma of patients with NDDs, suggesting its involvement in disease progression. As a critical regulator of neuroinflammation, CHI3-L1 modulates the activity of astrocyte and microglia, causing the production of pro-inflammatory cytokines that worsens disease progression. In addition to its involvement in disease pathophysiology, it has emerged as a potential biomarker for the diagnosis and monitoring of neurological diseases. However, significant knowledge gaps persist regarding its molecular mechanisms, interactions with inflammatory mediators, and influence on blood-brain barrier integrity. Therefore, this review highlights the emerging role of CHI3-L1 in neurodegeneration and describes future research approaches targeted at unlocking its therapeutic potential in treating NDDs.