NEIL1, short for Nei-like DNA Glycosylase 1, is a crucial enzyme in the base excision repair (BER) pathway. It specifically recognizes and removes oxidized bases, mainly oxidized pyrimidines, from DNA, thereby maintaining genomic integrity. The BER pathway is essential for repairing oxidatively modified base lesions, and NEIL1's role in this pathway is vital for human health and longevity [2,3]. Genetic models, such as knockout mice, have been valuable in studying NEIL1's function.

Knocking out neil1 in mice markedly suppresses tumorigenesis and enhances infiltration of CD8+ T cells in intestinal tumors, indicating its role in colorectal cancer initiation. NEIL1 directly forms a complex with SATB2/c-Myc to enhance the transcription of COL17A1, promoting the production of immunosuppressive cytokines in CRC cells [1]. Neil1 knockout mice are also >3-fold more susceptible to AFB1-induced carcinogenesis compared to wild-type or nucleotide excision repair-deficient Xpa-/-mice, suggesting its protective role against aflatoxin-induced hepatocellular carcinoma [5,6]. Moreover, Neil1-/-mice display an anxiety-mediated behavior, deficient recognitive memory, increased neuroinflammatory response, decreased neurogenesis, and impaired stress response, indicating its role in adult neurogenesis and resolution of neuroinflammation [4].

In conclusion, NEIL1 is essential for maintaining genomic integrity through its role in the BER pathway. Studies using NEIL1 knockout mouse models have revealed its significance in multiple disease areas, including colorectal cancer and hepatocellular carcinoma, as well as in neurogenesis and neuroinflammation. These findings enhance our understanding of the biological functions of NEIL1 and its implications for human health.