Ntf5, also known as neurotrophin-5, is a member of the neurotrophin protein family. Neurotrophins play crucial roles in the differentiation, survival, and function of vertebrate neurons [6]. They are involved in various neural-related pathways, and understanding Ntf5 is essential for grasping neural development and neurodegenerative disease mechanisms. Genetic models, such as KO/CKO mouse models, can be valuable in studying Ntf5.

In rotenone-induced neural degeneration, glial cells can affect retinal cell survival, and microglia-derived Ntf5 is upregulated, suggesting its positive role in this process [1]. In developing ovaries, the expression and regulation of Ntf5 vary between humans and mice, and activin A selectively regulates its expression in mice, indicating its significance in ovarian development [2]. In a mouse model of Stargardt-like macular dystrophy (STGD3), Ntf5 is among the genes with significant expression level changes, being upregulated [3]. In C8-B4 microglia transformed by repetitive low-dose lipopolysaccharide, Ntf5 is highly expressed along with other neuroprotective molecules, highlighting its potential neuroprotective function [4]. In female mice with surgically induced osteoarthritis, pain-associated genes including Ntf5 are significantly up-regulated at the time of established pain-like behavior, suggesting its involvement in pain-related responses [5]. Also, polyunsaturated fatty acids in egg yolk phospholipids may exert neuroprotective effects by upregulating Ntf5 in HT22 cells [7].

In conclusion, Ntf5 is involved in multiple biological processes including neural cell survival, ovarian development, neurodegenerative diseases, pain-related responses, and neuroprotection. Studies using mouse models have been instrumental in revealing these functions, which may contribute to understanding the mechanisms of related diseases and potentially developing new therapeutic strategies.

References:

1. Tawarayama, Hiroshi, Inoue-Yanagimachi, Maki, Himori, Noriko, Nakazawa, Toru. 2021. Glial cells modulate retinal cell survival in rotenone-induced neural degeneration. In Scientific reports, 11, 11159. doi:10.1038/s41598-021-90604-w. https://pubmed.ncbi.nlm.nih.gov/34045544/

2. Childs, Andrew J, Bayne, Rosemary A L, Murray, Alison A, Spears, Norah, Anderson, Richard A. . Differential expression and regulation by activin of the neurotrophins BDNF and NT4 during human and mouse ovarian development. In Developmental dynamics : an official publication of the American Association of Anatomists, 239, 1211-9. doi:10.1002/dvdy.22252. https://pubmed.ncbi.nlm.nih.gov/20175187/

3. Kuny, Sharee, Gaillard, Frédéric, Sauvé, Yves. 2012. Differential gene expression in eyecup and retina of a mouse model of Stargardt-like macular dystrophy (STGD3). In Investigative ophthalmology & visual science, 53, 664-75. doi:10.1167/iovs.11-8418. https://pubmed.ncbi.nlm.nih.gov/22199241/

4. Mizobuchi, Haruka, Yamamoto, Kazushi, Tsutsui, Shoko, Kohchi, Chie, Soma, Gen-Ichiro. 2020. A unique hybrid characteristic having both pro- and anti-inflammatory phenotype transformed by repetitive low-dose lipopolysaccharide in C8-B4 microglia. In Scientific reports, 10, 8945. doi:10.1038/s41598-020-65998-8. https://pubmed.ncbi.nlm.nih.gov/32488176/

5. von Loga, Isabell S, Batchelor, Vicky, Driscoll, Clare, Dell'Accio, Francesco, Vincent, Tonia L. 2020. Does Pain at an Earlier Stage of Chondropathy Protect Female Mice Against Structural Progression After Surgically Induced Osteoarthritis? In Arthritis & rheumatology (Hoboken, N.J.), 72, 2083-2093. doi:10.1002/art.41421. https://pubmed.ncbi.nlm.nih.gov/32602242/

6. Berkemeier, L R, Ozçelik, T, Francke, U, Rosenthal, A. . Human chromosome 19 contains the neurotrophin-5 gene locus and three related genes that may encode novel acidic neurotrophins. In Somatic cell and molecular genetics, 18, 233-45. doi:. https://pubmed.ncbi.nlm.nih.gov/1496419/

7. Li, Jingyu, Fang, Bing, Wu, Yao, Gao, Haina, Zhang, Ming. 2025. Investigating the neuroprotective effects of polyunsaturated fatty acids in egg yolk phospholipids upon oxidative damage in HT22 cells. In Food & function, , . doi:10.1039/d5fo00833f. https://pubmed.ncbi.nlm.nih.gov/40341910/