Ngfr-flox Mouse

Ngfr, also known as p75NTR, is the nerve growth factor receptor. It is a low-affinity receptor for all known mammalian neurotrophins, involved in pathways determining both neuron survival and death. It is also associated with the binding of Aβ peptides in Alzheimer's disease pathogenesis [2].

In melanoma, NGFR-positive small extracellular vesicles (sEVs) derived from metastatic melanoma cell lines promote lymphangiogenesis and metastasis. Ablation or inhibition of NGFR in sEVs reversed the lymphangiogenic phenotype, decreased lymph node metastasis, and extended survival in pre-clinical models. Also, in melanoma patients, NGFR expression was augmented in lymph node metastases, and the frequency of NGFR + metastatic melanoma cells in lymph nodes correlated with patient survival [1].

In colorectal cancer, overexpression of NGFR enhanced the apoptotic and autophagic effects of 5-fluorouracil, increasing chemosensitivity. NGFR elevated the expression of S100A9 after 5-FU treatment, and patients with NGFR + / S100A9 + had better survival [4].

In melanoma, a pre-existing NGFRhi population is refractory to T cells and BRAF + MEK inhibitors, and pharmacologic NGFR inhibition restores tumor sensitivity to T cell attack in vitro and in melanoma xenografts [3].

In Alzheimer's disease, the rs2072446 polymorphism in the NGFR gene was associated with an increased risk of sporadic Alzheimer's disease in the Chinese Han population and heavier Aβ burden in the ADNI cohort [5].

In conclusion, Ngfr plays crucial roles in multiple biological processes and disease conditions. Its functions in promoting metastasis in melanoma, influencing chemosensitivity in colorectal cancer, contributing to therapy resistance in melanoma, and being associated with Alzheimer's disease risk and Aβ deposition are revealed through various in vivo studies and genetic-based research. These findings highlight the importance of Ngfr-related KO or inhibition models in understanding disease mechanisms and potentially developing targeted therapies.