Homer1, a postsynaptic scaffolding protein, has multifaceted functions. It integrates different signal transduction pathways at the glutamatergic postsynaptic density (PSD), regulating motor and cognitive functions. It is involved in pathways such as modulating calcium signaling, regulating type I metabotropic glutamate receptor trafficking, and controlling long-term potentiation and dendritic spine growth [2].

In disease-related studies, Homer1 knock-down and over-expression mouse models have provided insights. In intracerebral hemorrhage (ICH) models, Homer1 over-expression promoted the conversion of A1 astrocytes to A2 astrocytes, inhibited MAPK signaling, and improved outcomes, while Homer1 knock-down had the opposite effects [1]. In middle cerebral artery occlusion (MCAO)-induced retinal ischemia models, over-expression of Homer1 protected retinal ganglion cells from pyroptosis by inhibiting endoplasmic reticulum stress-associated TXNIP/NLRP3 inflammasome activation [3]. In ischemic stroke models, Homer1 knockdown promoted neuronal death and neuroinflammation via enhancing necroptotic signaling pathways, while injection of Homer1 protein reduced necroptosis-induced brain injury [4].

In conclusion, Homer1 plays crucial roles in multiple biological processes, especially in protecting against inflammation and cell death in conditions like ICH, retinal ischemia, and ischemic stroke. The use of Homer1 knockout or knockdown mouse models has been instrumental in revealing its role in these disease-related processes, offering potential therapeutic targets for such conditions.

References:

1. Fei, Xiaowei, Dou, Ya-Nan, Wang, Li, Wei, Jialiang, Fei, Zhou. 2022. Homer1 promotes the conversion of A1 astrocytes to A2 astrocytes and improves the recovery of transgenic mice after intracerebral hemorrhage. In Journal of neuroinflammation, 19, 67. doi:10.1186/s12974-022-02428-8. https://pubmed.ncbi.nlm.nih.gov/35287697/

2. de Bartolomeis, Andrea, Barone, Annarita, Buonaguro, Elisabetta Filomena, Vellucci, Licia, Iasevoli, Felice. 2022. The Homer1 family of proteins at the crossroad of dopamine-glutamate signaling: An emerging molecular "Lego" in the pathophysiology of psychiatric disorders. A systematic review and translational insight. In Neuroscience and biobehavioral reviews, 136, 104596. doi:10.1016/j.neubiorev.2022.104596. https://pubmed.ncbi.nlm.nih.gov/35248676/

3. Lv, Weihao, Wu, Xiuquan, Dou, Yanan, Fei, Zhou, Fei, Fei. 2023. Homer1 Protects against Retinal Ganglion Cell Pyroptosis by Inhibiting Endoplasmic Reticulum Stress-Associated TXNIP/NLRP3 Inflammasome Activation after Middle Cerebral Artery Occlusion-Induced Retinal Ischemia. In International journal of molecular sciences, 24, . doi:10.3390/ijms242316811. https://pubmed.ncbi.nlm.nih.gov/38069134/

4. Lv, Weihao, Zhang, Qianqian, Li, Yuanming, Zhang, Lei, Fei, Zhou. 2023. Homer1 ameliorates ischemic stroke by inhibiting necroptosis-induced neuronal damage and neuroinflammation. In Inflammation research : official journal of the European Histamine Research Society ... [et al.], 73, 131-144. doi:10.1007/s00011-023-01824-x. https://pubmed.ncbi.nlm.nih.gov/38091015/