Multiple Interconnected Pathological Factors in Alzheimer’s Disease

Abstract

Alzheimer’s disease (AD), associated with degeneration of neurons and synapses in the brain, leads to motor impairment and eventual fatality. Neurodegeneration could be related to various interconnected features, including (i) plaque formation from amyloid-β (Aβ) peptide fragments, (ii) metal ion dyshomeostasis and miscompartmentalization, as well as (iii) inflammation and increased oxidative stress due to overproduction of reactive oxygen species (ROS). The inter-relations between some of these pathological factors have been investigated. Metals are found entangled in the Aβ plaque and likely contribute to Aβ neurotoxicity and oxidative stress. ROS have been shown to increase the rate of Aβ plaque formation. Our understanding of the correlation between these elements and AD neuropathogenesis has been very limited, however. There is currently no cure for AD; therapies are focused on symptomatic relief targeting the decrease in the levels of acetylcholine, only one of the multiple factors causing the disease.1 To find a cure for AD, we require a better understanding of the relationship between the various causative factors of this devastating disease. Towards this goal, we need suitable chemical tools capable of targeting and regulating its multiple underlying factors simultaneously.1,2 Herein, our rational design and preparation of our chemical tools will be discussed with our investigations of their reactivities with targets in vitro as well as their efficacy in vivo.