Linking Oxidative Stress and Proteinopathy in Alzheimer’s Disease

Abstract

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.

Probiotics for Alzheimer’s Disease: A Systematic Review

“…In the study by Kanamaru and co-workers (2015), they report the enhancement of oxidative stress and Aβ deposition in double transgenic mouse model of AD [ 46 ]. This oxidation is suggested to be the pathological marker in the disease’s progression of AD patients by increasing Aβ, tau hyperphosphorylation, and neuronal death [ 47 ]. Although the comprehensive etiopathogenesis of AD remains unclear, understanding the roles and mechanisms of gut microbiota in the AD pathogenesis can help develop promising strategies in the AD treatments.…”

Disentangling Mitochondria in Alzheimer’s Disease

“…Another cardinal feature of AD pathogenesis is the extent and accumulation of oxidative damage that takes place alongside alterations in glucose metabolism and mitochondrial dysfunction in the brains of transgenic animal models and patients with AD [ 134 , 135 , 136 , 137 , 138 , 139 , 140 , 141 ]. Increased free radicals and carbonylated proteins were observed in concert with increased mitochondrial dysfunction in young transgenic AD mice [ 38 ].…”

“…Increased free radicals and carbonylated proteins were observed in concert with increased mitochondrial dysfunction in young transgenic AD mice [ 38 ]. Oxidative stress is consistently observed in AD [ 141 , 142 , 143 , 144 , 145 ]. Increased lipid peroxidation precedes amyloid plaque formation in an animal model of AD and is a recurrent feature of preclinical AD [ 146 , 147 , 148 , 149 ].…”

Potentiating the Benefits of Melatonin through Chemical Functionalization: Possible Impact on Multifactorial Neurodegenerative Disorders

“…In the particular case of NDD, the multifunctionality of the desired therapeutic one-molecule multiple-target chemicals should include some of the following effects: (i) inhibition of acetylcholinesterase (AChE); (ii) inhibition of monoamine oxidase (MAO); (iii) inhibition of catechol O-methyltransferase (COMT); (iv) antioxidant behavior; (v) free radical scavenging activity; and (vi) metal chelating power [ 1 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 ].…”