Yin Jun, Chen Hsueh-Ling, Grigsby-Brown Anna, He Yi, Cotten Myriam L, Short Jacob, Dermady Aidan, Lei Jingce, Gibbs Mary, Cheng Ethan S, Zhang Dean, Long Caixia, Tabet Jennifer, Xu Lele, Zhong Tiffany, Abzalimov Rinat, Haider Mariam, Sun Rong, He Ye, Zhou Qiangjun, Tjandra Nico, Yuan Quan
Dendrite Morphogenesis and Plasticity Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Fermentation Facility, Biochemistry and Biophysics Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Sci Adv. 2025 Aug;11(31):eadv2902. doi: 10.1126/sciadv.adv2902. Epub 2025 Aug 1.
Glia-derived secretory factors are essential for brain development, physiology, and homeostasis, with their dysfunction linked to a variety of neurological disorders. Through genetic and biochemical approaches, we identified odorant binding protein 44a (Obp44a), a noncanonical α-helical fatty acid binding protein (FABP) highly expressed in central nervous system glia. Obp44a binds long-chain fatty acids and shuttles between glia and neurons, acting as a secretory lipid chaperone and scavenger to support lipid storage, efflux, and redox homeostasis. Notably, Obp44a is recruited to apoptotic cells and injured axons, especially when glial engulfment is impaired, demonstrating its role in lipid waste management and clearance of cellular debris during development and in pathological states. Our findings highlight FABPs' importance in regulating brain lipid dynamics and neuronal response to stress and injury. By visualizing FABP function in vivo, this study provides insights into how defective lipid regulation may contribute to neuronal stress and disease progression.
神经胶质细胞衍生的分泌因子对大脑发育、生理功能和内环境稳定至关重要，其功能障碍与多种神经疾病相关。通过遗传学和生物化学方法，我们鉴定出气味结合蛋白44a（Obp44a），这是一种非典型的α-螺旋脂肪酸结合蛋白（FABP），在中枢神经系统神经胶质细胞中高度表达。Obp44a结合长链脂肪酸，并在神经胶质细胞和神经元之间穿梭，作为一种分泌性脂质伴侣和清除剂，以支持脂质储存、流出和氧化还原稳态。值得注意的是，Obp44a被募集到凋亡细胞和受损轴突处，尤其是在神经胶质细胞吞噬功能受损时，这表明它在发育过程和病理状态下的脂质废物管理和细胞碎片清除中发挥作用。我们的研究结果突出了FABP在调节大脑脂质动态以及神经元对应激和损伤反应中的重要性。通过在体内观察FABP的功能，本研究为脂质调节缺陷如何导致神经元应激和疾病进展提供了见解。
