Figures & data
Figure 1 Overview of neuronal microtubule dysfunction pathways leading to neurodegeneration.
Notes: Studies have demonstrated that disruption of microtubule structure and function has downstream consequences that ultimately lead to neurodegeneration and cell death. Among those effects initiated by microtubule dysfunction are the activation of cell death signaling cascades, axonal degeneration, dysregulation of axonal transport (both retrograde and anterograde transport) and the loss of synaptic structures. This diagram traces the downstream effects of those actions, including the critical events surrounding protein aggregation, that are responsible for the cell death and loss of synaptic transmission that represent critical events leading to neurodegeneration. Those pathways known to be impacted by the neuroprotective drug, davunetide, are shown in red. As described in the associated text, davunetide directly impacts pathways relevant to neurodegenerative disease at multiple levels in this schema. Studies have shown protection of microtubules against toxic insult, reduction in tau phosphorylation, reductions in aggregated proteins in animal models of disease, modulation of intracellular signaling cascades critical to cell survival, and markers of synaptic plasticity. These molecular events triggered by davunetide ultimately result in maintenance of neurotransmission and cell viability which in turn are manifested as a drug-dependent impact on disease progression.
