Oxidative species-induced excitonic transport in tubulin aromatic networks: Potential implications for neurodegenerative disease

Oxidative stress is a pathological hallmark of neurodegenerative tauopathic disorders such as Alzheimer's disease and Parkinson's disease-related dementia, which are characterized by altered forms of the microtubule-associated protein (MAP) tau. MAP tau is a key protein in stabilizing the microtubule architecture that regulates neuron morphology and synaptic strength. The precise role of reactive oxygen species (ROS) in the tauopathic disease process, however, is poorly understood. It is known that the production of ROS by mitochondria can result in ultraweak photon emission (UPE) within cells. One likely absorber of these photons is the microtubule cytoskeleton, as it forms a vast network spanning neurons, is highly co-localized with mitochondria, and shows a high density of aromatic amino acids. Functional microtubule networks may traffic this ROS-generated endogenous photon energy for cellular signaling, or they may serve as dissipaters/conduits of such energy. Experimentally, after in vitro exposure to exogenous photons, microtubules have been shown to reorient and reorganize in a dose-dependent manner with the greatest effect being observed around 280 nm, in the tryptophan and tyrosine absorption range. In this paper, recent modeling efforts based on ambient temperature experiment are presented, showing that tubulin polymers can feasibly absorb and channel these photoexcitations via resonance energy transfer, on the order of dendritic length scales. Since microtubule networks are compromised in tauopathic diseases, patients with these illnesses would be unable to support effective channeling of these photons for signaling or dissipation. Consequent emission surplus due to increased UPE production or decreased ability to absorb and transfer may lead to increased cellular oxidative damage, thus hastening the neurodegenerative process.