中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (7): 1454-1461.doi: 10.4103/1673-5374.330588

• 综述:脑损伤修复保护与再生 • 上一篇    下一篇

缺血和创伤性脑损伤及视网膜病变的有效治疗靶点:Homer信号通路

  

  • 出版日期:2022-07-15 发布日期:2022-01-15

Homer signaling pathways as effective therapeutic targets for ischemic and traumatic brain injuries and retinal lesions

Xiu-Quan Wu1, #, Ning Su2, #, Zhou Fei1, *, Fei Fei3, *   

  1. 1Department of Neurosurgery, Xijing Hospital, the Fourth Military Medical University, Xi’an, Shaanxi Province, China; 2Department of Radiation Oncology, Xijing Hospital, the Fourth Military Medical University, Xi’an, Shaanxi Province, China; 3Department of Ophthalmology, Xijing Hospital, the Fourth Military Medical University, Xi’an, Shaanxi Province, China
  • Online:2022-07-15 Published:2022-01-15
  • Contact: Fei Fei, MD, feifeifmmu@126.com; Zhou Fei, MD, feizhou@fmmu.edu.cn.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, Nos. 81600738 (to FF), 81771239 (to ZF), 81801300 (to NS).

摘要: https://orcid.org/0000-0001-6194-5663 (Fei Fei); https://orcid.org/0000-0003-3276-6345 (Zhou Fei) 

Abstract: Ischemic and traumatic insults to the central nervous system account for most serious acute and fatal brain injuries and are usually characterized by primary and secondary damage. Secondary damage presents the greatest challenge for medical staff; however, there are currently few effective therapeutic targets for secondary damage. Homer proteins are postsynaptic scaffolding proteins that have been implicated in ischemic and traumatic insults to the central nervous system. Homer signaling can exert either positive or negative effects during such insults, depending on the specific subtype of Homer protein. Homer 1b/c couples with other proteins to form postsynaptic densities, which form the basis of synaptic transmission, while Homer1a expression can be induced by harmful external factors. Homer 1c is used as a unique biomarker to reveal alterations in synaptic connectivity before and during the early stages of apoptosis in retinal ganglion cells, mediated or affected by extracellular or intracellular signaling or cytoskeletal processes. This review summarizes the structural features, related signaling pathways, and diverse roles of Homer proteins in physiological and pathological processes. Upregulating Homer1a or downregulating Homer1b/c may play a neuroprotective role in secondary brain injuries. Homer also plays an important role in the formation of photoreceptor synapses. These findings confirm the neuroprotective effects of Homer, and support the future design of therapeutic drug targets or gene therapies for ischemic and traumatic brain injuries and retinal disorders based on Homer proteins.

Key words: brain injury, calcium signaling, cerebral ischemia, dendritic spine, glutamate receptor, Homer scaffolding protein, neuron, neuroprotection, retinal ganglion cell, review, traumatic brain injury