Ngfr, also known as p75NTR, is the low-affinity receptor for all known mammalian neurotrophins. It is involved in pathways determining both neuron survival and death, and also plays a role in cell death and survival processes in general [2,4]. It can be found in the context of multiple biological processes and diseases due to its associations with various signaling pathways, such as those related to neurotrophin-mediated functions. Genetic models, like gene knockout models, can be used to study its functions in vivo.

In melanoma, ablation or inhibition of NGFR in small extracellular vesicles (sEVs) derived from metastatic melanoma cell lines reversed the lymphangiogenic phenotype, decreased lymph node metastasis, and extended survival. This shows that NGFR in melanoma-derived sEVs plays a role in reinforcing lymph node pre-metastatic niche formation and metastasis [1]. In colorectal cancer, transfection of NGFR into cells increased the chemosensitivity to 5-fluorouracil, as it enhanced apoptotic and autophagic effects via the activation of S100A9 [4]. In oral cancer, targeted knockdown of NGFR inhibited metastasis, perineural invasion (PNI), and mechanical allodynia, indicating its role in these processes [6]. In Alzheimer's disease, the polymorphism rs2072446 in the NGFR gene was associated with an increased risk of sporadic Alzheimer's disease and heavier amyloid-β burden in certain populations [5]. Pharmacologic NGFR inhibition restored tumor sensitivity to T-cell attack in melanoma, suggesting its role in mediating tumor and immune therapy resistance [3].

In conclusion, Ngfr is a key receptor involved in multiple biological processes, with its functions studied through various genetic models. It plays important roles in diseases such as melanoma, colorectal cancer, oral cancer, and Alzheimer's disease. The study of Ngfr using knockout or knockdown models has provided insights into its functions in disease-related processes, offering potential directions for therapeutic interventions.

References:

1. García-Silva, Susana, Benito-Martín, Alberto, Nogués, Laura, Lyden, David, Peinado, Héctor. 2021. Melanoma-derived small extracellular vesicles induce lymphangiogenesis and metastasis through an NGFR-dependent mechanism. In Nature cancer, 2, 1387-1405. doi:10.1038/s43018-021-00272-y. https://pubmed.ncbi.nlm.nih.gov/34957415/

2. Bruno, Francesco, Abondio, Paolo, Montesanto, Alberto, Bruni, Amalia C, Maletta, Raffaele. 2023. The Nerve Growth Factor Receptor (NGFR/p75NTR): A Major Player in Alzheimer's Disease. In International journal of molecular sciences, 24, . doi:10.3390/ijms24043200. https://pubmed.ncbi.nlm.nih.gov/36834612/

3. Boshuizen, Julia, Vredevoogd, David W, Krijgsman, Oscar, Boland, Genevieve M, Peeper, Daniel S. 2020. Reversal of pre-existing NGFR-driven tumor and immune therapy resistance. In Nature communications, 11, 3946. doi:10.1038/s41467-020-17739-8. https://pubmed.ncbi.nlm.nih.gov/32770055/

4. Chen, Hao, Huang, Jintuan, Chen, Chunyu, Liao, Yi, Yang, Zuli. 2021. NGFR Increases the Chemosensitivity of Colorectal Cancer Cells by Enhancing the Apoptotic and Autophagic Effects of 5-fluorouracil via the Activation of S100A9. In Frontiers in oncology, 11, 652081. doi:10.3389/fonc.2021.652081. https://pubmed.ncbi.nlm.nih.gov/33996571/

5. He, Chen-Yang, Wang, Zuo-Teng, Shen, Ying-Ying, Zeng, Fan, Wang, Yan-Jiang. 2022. Association of rs2072446 in the NGFR gene with the risk of Alzheimer's disease and amyloid-β deposition in the brain. In CNS neuroscience & therapeutics, 28, 2218-2229. doi:10.1111/cns.13965. https://pubmed.ncbi.nlm.nih.gov/36074475/

6. Doan, Coleen, Aouizerat, Bradley E, Ye, Yi, Slater, Jason M, Viet, Chi T. 2022. Neurotrophin Pathway Receptors NGFR and TrkA Control Perineural Invasion, Metastasis, and Pain in Oral Cancer. In Advanced biology, 6, e2200190. doi:10.1002/adbi.202200190. https://pubmed.ncbi.nlm.nih.gov/35925599/