摘要
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.
基金
supported by FIS PI16/00786(2016)and FIS PI19/00377(2019)grants
the Ministerio de Sanidad,Spain and the Fondo Europeo de Desarrollo Regional(FEDER Unión Europea)
Spanish Ministry of Education,Culture and Sport.This activity has been co-financed by the European Regional Development Fund(ERDF)and by the Regional Ministry of Economic Transformation,Industry,Knowledge and Universities of the Junta de Andalucía,within the framework of the ERDF Andalusia operational program 2014-2020 Thematic objective“01-Reinforcement of research,technological development and innovation”through the reference research project CTS-5725 and PY18-850(to JASA).
