Neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and amyotrophic lateral
sclerosis cause damage and gradual loss of neurons affecting the central nervous system. Neurodegenerative
diseases are most commonly seen in the ageing process. Ageing causes increased reactive
oxygen species and decreased mitochondrial ATP generation, resulting in redox imbalance and
oxidative stress. Oxidative stress-generated free radicals cause damage to membrane lipids containing
polyunsaturated fatty acids, leading to the formation of toxic lipid aldehyde products such as 4-
hydroxynonenal and malondialdehyde. Several studies have shown that lipid peroxidation-derived
aldehyde products form adducts with cellular proteins, altering their structure and function. Thus,
these lipid aldehydes could act as secondary signaling intermediates, modifying important metabolic
pathways, and contributing to the pathophysiology of several human diseases, including neurodegenerative
disorders. Additionally, they could serve as biomarkers for disease progression. This narrative
review article discusses the biological and clinical significance of oxidative stress-mediated lipid
peroxidation-derived lipid aldehydes in the pathophysiology of various neurodegenerative diseases.