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.
Highlights
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
Based on postmortem data and experimental studies carried out using cell lines, primary culture of hippocampal neurons, and transgenic animal models, it has been prominently suggested that Aβ peptide oligomers can interact with numerous astrocytic, microglial, and neuronal synaptic proteins, including α7- acetylcholine receptors (AChRs) and Nmethyl-D-aspartate receptors (NMDARs); this, in turn, triggers a series of toxic synaptic events [58,59,60,61]
The results suggested a three-fold higher binding activity between advanced glycation end products (AGEs) and ApoE4 compared to binding activity between AGE and ApoE3, which signifies the pathogenic risk associated with ApoE4 in the case of fAD
Summary
Reactive oxygen species (ROS) result from normal daily cellular metabolism. Research conducted in the last two decades has clarified the role of ROS as secondary signaling molecules that regulate various biological and physiological processes, including proliferation, host defense, and gene expression [1,2]. Amongst electron transport chain (ETC) of mitochondria produces superoxide radicals at respiravarious intracellular antioxidant enzymes, five have been mainly discussed in physiological tory complexes I and III of the oxidative phosphorylation (OXPHOS) pathway through conditions, i.e., (i) Cu/Zn-superoxide dismutase (Cu/Zn-SOD, SOD1) in the cytosol, (ii) the single-electron leak [2,6]. Processing and thereby triggers amyloid-beta (Aβ) generation [21,22] These elevations in ROS are the results of protein aggregation and corresponding neuronal damage, which in turn activates disease-associated microglia via damage-associated molecular patterns [23]. Keeping this in mind, in this review, we sought to analyze the myriad interactions between oxygen radicals and toxic protein oligomers in the context of AD to understand their importance in disease pathogenesis. We discuss the role of microbiota in altering redox balance and its consequences concerning Aβ production and tau hyperphosphorylation
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
