Linking Oxidative Stress and Proteinopathy in Alzheimer’s Disease

• Published in: Antioxidants Vol. 10; no. 8; p. 1231
• Main Authors: Sharma, Chanchal, Kim, Sang Ryong
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 30.07.2021; MDPI
• Subjects: Aging; Alzheimer's disease; amyloidopathy; Antioxidants; DNA damage; Enzymes; Free radicals; Gene expression; Intermediates; Lipid peroxidation; Lipids; Mitochondria; Mitochondrial DNA; Neurodegeneration; Neurodegenerative diseases; Neuroprotection; Neurotoxicity; Oxidation; Oxidative stress; Pathogenesis; Phosphorylation; Physiology; proteinopathy; Proteins; Reactive oxygen species; Review; Signal transduction; Tau protein; tauopathy; β-Amyloid
• ISSN: 2076-3921; 2076-3921
• DOI: 10.3390/antiox10081231

Proteinopathy and excessive production of reactive oxygen species (ROS), which are the principal features observed in the Alzheimer’s disease (AD) brain, contribute to neuronal toxicity. β-amyloid and tau are the primary proteins responsible for the proteinopathy (amyloidopathy and tauopathy, respectively) in AD, which depends on ROS production; these aggregates can also generate ROS. These mechanisms work in concert and reinforce each other to drive the pathology observed in the aging brain, which primarily involves oxidative stress (OS). This, in turn, triggers neurodegeneration due to the subsequent loss of synapses and neurons. Understanding these interactions may thus aid in the identification of potential neuroprotective therapies that could be clinically useful. Here, we review the role of β-amyloid and tau in the activation of ROS production. We then further discuss how free radicals can influence structural changes in key toxic intermediates and describe the putative mechanisms by which OS and oligomers cause neuronal death.