Villalón-García Irene, Povea-Cabello Suleva, Álvarez-Córdoba Mónica, Talaverón-Rey Marta, Suárez-Rivero Juan M, Suárez-Carrillo Alejandra, Munuera-Cabeza Manuel, Reche-López Diana, Cilleros-Holgado Paula, Piñero-Pérez Rocío, Sánchez-Alcázar José A
Centro Andaluz de Biología del Desarrollo (CABD-CSIC-Universidad Pablo de Olavide de Sevilla), and Centro de Investigación Biomédica en Red: Enfermedades Raras, Instituto de Salud Carlos III, Sevilla, Spain.
Neural Regen Res. 2023 Jun;18(6):1196-1202. doi: 10.4103/1673-5374.358614.
Lipid peroxidation and iron accumulation are closely associated with neurodegenerative diseases, such as Alzheimer's, Parkinson's, and Huntington's diseases, or neurodegeneration with brain iron accumulation disorders. Mitochondrial dysfunction, lipofuscin accumulation, autophagy disruption, and ferroptosis have been implicated as the critical pathomechanisms of lipid peroxidation and iron accumulation in these disorders. Currently, the connection between lipid peroxidation and iron accumulation and the initial cause or consequence in neurodegeneration processes is unclear. In this review, we have compiled the known mechanisms by which lipid peroxidation triggers iron accumulation and lipofuscin formation, and the effect of iron overload on lipid peroxidation and cellular function. The vicious cycle established between both pathological alterations may lead to the development of neurodegeneration. Therefore, the investigation of these mechanisms is essential for exploring therapeutic strategies to restrict neurodegeneration. In addition, we discuss the interplay between lipid peroxidation and iron accumulation in neurodegeneration, particularly in PLA2G6-associated neurodegeneration, a rare neurodegenerative disease with autosomal recessive inheritance, which belongs to the group of neurodegeneration with brain iron accumulation disorders.
脂质过氧化和铁蓄积与神经退行性疾病密切相关，如阿尔茨海默病、帕金森病和亨廷顿病，或与脑铁蓄积障碍相关的神经退行性变。线粒体功能障碍、脂褐素蓄积、自噬破坏和铁死亡被认为是这些疾病中脂质过氧化和铁蓄积的关键发病机制。目前，脂质过氧化与铁蓄积之间的联系以及在神经退行性变过程中的初始原因或后果尚不清楚。在本综述中，我们汇总了脂质过氧化引发铁蓄积和脂褐素形成的已知机制，以及铁过载对脂质过氧化和细胞功能的影响。这两种病理改变之间形成的恶性循环可能导致神经退行性变的发展。因此，对这些机制的研究对于探索限制神经退行性变的治疗策略至关重要。此外，我们还讨论了脂质过氧化与铁蓄积在神经退行性变中的相互作用，特别是在与磷脂酶A2G6相关的神经退行性变中，这是一种罕见的常染色体隐性遗传神经退行性疾病，属于脑铁蓄积障碍相关的神经退行性变类别。
