Fabp7-KO Mouse

Fabp7, also known as brain-typed fatty acid-binding protein, is an intracellular protein. It is involved in the uptake, transportation, metabolism, and storage of fatty acids (FAs). Fatty acid-binding proteins (FABPs) like Fabp7 facilitate FAs transport to different cell organelles, modulating their metabolism and mediating other physiological activities. Lipid signaling functions associated with Fabp7 are related to metabolic pathways impacting disease pathologies such as cancer, autism, and schizophrenia [1,2,3].

In cancer, Fabp7 silencing or pharmacological inhibition in cell lines and xenograft models suggest it promotes cell growth, migration, invasion, and tumour formation [2]. In glioblastoma stem cells, it is considered an attractive metabolic target [4]. In neurodegenerative diseases, in ALS animal models, FABP7 upregulation in astrocytes promotes a pro-inflammatory response detrimental to motor neuron survival, and silencing endogenous FABP7 decreases toxicity [5]. In Alzheimer's disease, amyloid β treatment induces FABP7 upregulation in astrocytes, and its overexpression drives an NF-κB-driven inflammatory response [6]. In multiple system atrophy, FABP7 forms hetero-aggregates with α-synuclein, and epsin-2 may regulate their propagation [7]. In glioma, nuclear FABP7 promotes cell proliferation through caveolae formation [8]. In astrocytes, FABP7 knockout leads to decreased lipid droplet (LD) accumulation, elevated ROS toxicity, and apoptosis under ROS stress, while overexpression has the opposite effect [9]. In autism organoids, FABP7 deficiency triggers premature neural differentiation, and regulation of the FABP7/MEK pathway reverses this [10].

In summary, Fabp7 plays crucial roles in multiple biological processes and diseases. Through gene knockout and other functional studies in various models, its functions in cancer, neurodegenerative diseases, and autism-related neural differentiation have been revealed. These findings contribute to understanding the underlying mechanisms of these diseases and may provide potential therapeutic targets.

References:

1. Kagawa, Yoshiteru, Umaru, Banlanjo A, Ariful, Islam, Ogata, Masaki, Owada, Yuji. 2018. Role of FABP7 in tumor cell signaling. In Advances in biological regulation, 71, 206-218. doi:10.1016/j.jbior.2018.09.006. https://pubmed.ncbi.nlm.nih.gov/30245263/

2. George Warren, William, Osborn, Myles, Yates, Andrew, O'Sullivan, Saoirse E. 2024. The emerging role of fatty acid binding protein 7 (FABP7) in cancers. In Drug discovery today, 29, 103980. doi:10.1016/j.drudis.2024.103980. https://pubmed.ncbi.nlm.nih.gov/38614160/

3. Lenz, Stefan, Bodnariuc, Iulia, Renaud-Young, Margaret, Butler, Tanille M, MacCallum, Justin L. 2023. Understanding FABP7 binding to fatty acid micelles and membranes. In Biophysical journal, 122, 603-615. doi:10.1016/j.bpj.2023.01.023. https://pubmed.ncbi.nlm.nih.gov/36698315/

4. Sun, Yanfei, Mu, Guangjing, Xue, Zhiwei, Ni, Shilei, Han, Mingzhi. . Polyunsaturated fatty acid-binding protein FABP7, an attractive metabolic target for inhibition of glioblastoma stem cells. In Neuro-oncology, 26, 587-589. doi:10.1093/neuonc/noad238. https://pubmed.ncbi.nlm.nih.gov/38244234/

5. Killoy, Kelby M, Harlan, Benjamin A, Pehar, Mariana, Vargas, Marcelo R. 2020. FABP7 upregulation induces a neurotoxic phenotype in astrocytes. In Glia, 68, 2693-2704. doi:10.1002/glia.23879. https://pubmed.ncbi.nlm.nih.gov/32619303/

6. Hamilton, Haylee L, Kinscherf, Noah A, Balmer, Garrett, Vargas, Marcelo R, Pehar, Mariana. 2023. FABP7 drives an inflammatory response in human astrocytes and is upregulated in Alzheimer's disease. In GeroScience, 46, 1607-1625. doi:10.1007/s11357-023-00916-0. https://pubmed.ncbi.nlm.nih.gov/37688656/

7. Cheng, An, Kawahata, Ichiro, Wang, Yifei, Sasaki, Takuya, Fukunaga, Kohji. . Epsin2, a novel target for multiple system atrophy therapy via α-synuclein/FABP7 propagation. In Brain : a journal of neurology, 146, 3172-3180. doi:10.1093/brain/awad137. https://pubmed.ncbi.nlm.nih.gov/37082980/

8. Kagawa, Yoshiteru, Umaru, Banlanjo Abdulaziz, Kanamori, Masayuki, Tominaga, Teiji, Owada, Yuji. 2021. Nuclear FABP7 regulates cell proliferation of wild-type IDH1 glioma through caveolae formation. In Molecular oncology, 16, 289-306. doi:10.1002/1878-0261.13130. https://pubmed.ncbi.nlm.nih.gov/34716958/

9. Islam, Ariful, Kagawa, Yoshiteru, Miyazaki, Hirofumi, Yamamoto, Yui, Owada, Yuji. 2019. FABP7 Protects Astrocytes Against ROS Toxicity via Lipid Droplet Formation. In Molecular neurobiology, 56, 5763-5779. doi:10.1007/s12035-019-1489-2. https://pubmed.ncbi.nlm.nih.gov/30680690/

10. Han, Xiao, He, Yuanlin, Wang, Yuanhao, Liu, Yan, Hu, Zhibin. 2024. Deficiency of FABP7 Triggers Premature Neural Differentiation in Idiopathic Normocephalic Autism Organoids. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 12, e2406849. doi:10.1002/advs.202406849. https://pubmed.ncbi.nlm.nih.gov/39556706/