Alshahrani Sultan M, Al-Kuraishy Hayder M, Al-Gareeb Ali I, Albuhadily Ali K, Shokr Mustafa M, Kadasah Sultan F, Alexiou Athanasios, Papadakis Marios, El-Saber Batiha Gaber
College of Pharmacy, King Khalid University, Abha, 6144, Saudi Arabia; King Salman Center for Disability Research, Riyadh, 11614, Saudi Arabia.
Department of Clinical Pharmacology and Medicine, College of Medicine, Mustansiriyah University, Iraq.
Eur J Pharmacol. 2025 Sep 5;1002:177830. doi: 10.1016/j.ejphar.2025.177830. Epub 2025 Jun 6.
Parkinson's disease (PD) is the second most common neurodegenerative disease that represents the commonest movement disorder in the elderly population. PD neuropathology is due to the progressive deposition of mutant alpha synuclein (α-Syn) in the dopaminergic neurons (DNs) of the substantia nigra pars compacta (SNpc). Additionally, amyloid protein (Aβ) and tau protein, which are the hallmarks of Alzheimer's disease (AD), are also involved in PD and the development of PD-related dementia. Notably, α-Syn, Aβ, tau protein, and neuronal cholesterol metabolism are regulated by a transmembrane protein, low-density lipoprotein receptor-related protein 1 (LRP1), which is highly expressed in the SNpc and mediates the transmission and seeding of α-Syn in the brain. It has been reported that deletion of the LRP1 gene protects against the development and progression of PD. However, LRP1 has a neuroprotective effect against AD neuropathology by improving Aβ clearance across the blood-brain barrier (BBB) and enhancing tau protein proteolysis. Nevertheless, the exact role of LRP1 in PD neuropathology, mostly about α-Syn, is not completely explained. Therefore, this review aims to discuss and explain the role of LRP1 in PD and how targeting neuronal LRP1 may be helpful in the management of PD. In this review, online databases were involved by searching Scopus, Web of Science, and other search engine to detect the relationship between the expression of LRP1 and the pathogenesis of PD.
帕金森病（PD）是第二常见的神经退行性疾病，也是老年人群中最常见的运动障碍。PD的神经病理学是由于突变的α-突触核蛋白（α-Syn）在黑质致密部（SNpc）的多巴胺能神经元（DNs）中进行性沉积所致。此外，作为阿尔茨海默病（AD）标志的淀粉样蛋白（Aβ）和tau蛋白也与PD及PD相关痴呆的发生发展有关。值得注意的是，α-Syn、Aβ、tau蛋白和神经元胆固醇代谢受一种跨膜蛋白——低密度脂蛋白受体相关蛋白1（LRP1）的调节，LRP1在SNpc中高度表达，并介导α-Syn在大脑中的传递和播种。据报道，LRP1基因的缺失可预防PD的发生和进展。然而，LRP1通过改善Aβ穿过血脑屏障（BBB）的清除并增强tau蛋白的蛋白水解作用，对AD神经病理学具有神经保护作用。尽管如此，LRP1在PD神经病理学中的确切作用，主要是关于α-Syn的作用，尚未完全阐明。因此，本综述旨在讨论和解释LRP1在PD中的作用，以及靶向神经元LRP1如何有助于PD的管理。在本综述中，通过搜索Scopus、Web of Science和其他搜索引擎等在线数据库，来检测LRP1的表达与PD发病机制之间的关系。
