The functionality of the axon and the presynaptic terminal is critically dependent on axonal trafficking of materials (protein, mRNA, lipids) and organelles such as mitochondria. Moreover, retrograde transport of target-derived signals, particularly neurotrophic proteins, is essential for neuronal survival and plasticity [33]. Recent work has utilized microfluidic devices for single-molecule imaging of retrograde axonal transport of NGF [34] and dendrite-to-nucleus signaling of brain-derived neurotrophic factor (BDNF) [35]. Defects in axonal transport play an important role in pathogenesis of neurodegenerative diseases [36]. β-amyloid peptide (Aβ) and Tau are central pathophysiological molecules in Alzheimer’s disease. Using microfluidic devices, it has been shown that both Aβ [37] and Tau [38] impair axonal transport of mitochondria, and that Aβ also impairs retrograde axonal transport of BDNF and its receptor TrkB [39]. Interestingly, misfolding proteins that are characteristic for many neurodegenerative diseases appear to propagate between neurons in a prion-like fashion. Microfluidic devices provide an effective means to study neuron-to-neuron propagation mechanisms in vitro, as shown by a recent study addressing anterograde propagation of α-synuclein fibrils [40].
