Dedoni Simona, Avdoshina Valeria, Olianas Maria C, Onali Pierluigi
Department of Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology, University of Cagliari, 09142 Cagliari, Italy.
Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA.
Front Biosci (Landmark Ed). 2025 Apr 30;30(5):28245. doi: 10.31083/FBL28245.
Lysophosphatidic acid (LPA), a bioactive lipid molecule, has been identified as a critical regulator of several cellular processes in the central nervous system, with significant impacts on neuronal function, synaptic plasticity, and neuroinflammatory responses. While Alzheimer's disease, Multiple Sclerosis, and Parkinson's disease have garnered considerable attention due to their incidence and socioeconomic significance, many additional neurological illnesses remain unclear in terms of underlying pathophysiology and prospective treatment targets. This review synthesizes evidence linking LPA's function in neurological diseases such as traumatic brain injury, spinal cord injury, cerebellar ataxia, cerebral ischemia, seizures, Huntington's disease, amyotrophic lateral sclerosis, Hutchinson-Gilford progeria syndrome, autism, migraine, and human immunodeficiency virus (HIV)-associated complications Despite recent advances, the specific mechanisms underlying LPA's actions in various neurological disorders remain unknown, and further research is needed to understand the distinct roles of LPA across multiple disease conditions, as well as to investigate the therapeutic potential of targeting LPA receptors in these pathologies. The purpose of this review is to highlight the multiple functions of LPA in the aforementioned neurological diseases, which frequently share the same poor prognosis due to a scarcity of truly effective therapies, while also evaluating the role of LPA, its receptors, and signaling as promising actors for the development of alternative therapeutic strategies to those proposed today.
溶血磷脂酸(LPA)是一种生物活性脂质分子,已被确定为中枢神经系统中多种细胞过程的关键调节因子,对神经元功能、突触可塑性和神经炎症反应有重大影响。虽然阿尔茨海默病、多发性硬化症和帕金森病因其发病率和社会经济意义而备受关注,但许多其他神经系统疾病在潜在病理生理学和潜在治疗靶点方面仍不明确。本综述综合了有关LPA在诸如创伤性脑损伤、脊髓损伤、小脑共济失调、脑缺血、癫痫、亨廷顿舞蹈症、肌萎缩侧索硬化症、哈钦森-吉尔福德早衰综合征、自闭症、偏头痛以及人类免疫缺陷病毒(HIV)相关并发症等神经系统疾病中功能的证据。尽管最近有进展,但LPA在各种神经系统疾病中作用的具体机制仍不清楚,需要进一步研究以了解LPA在多种疾病状态下的不同作用,以及研究在这些病理情况下靶向LPA受体的治疗潜力。本综述的目的是强调LPA在上述神经系统疾病中的多种功能,这些疾病由于缺乏真正有效的治疗方法,常常具有相同的不良预后,同时还评估LPA及其受体和信号传导作为有前景的因素在开发替代当今所提出治疗策略方面的作用。