Axonal transport is essential for the maintenance of neuronal function and deficits in transport are known to result in neuronal degeneration in several areas of the nervous systems (1). For example, an Alzheimer’s disease (AD) mutant of amyloid precursor protein (APP) or APP overexpression, causes a deficit in axonal transport of nerve growth factor (NGF), which leads to degeneration of basal forebrain cholinergic neurons and contribute to early AD-like symptoms observed in individuals affected by Down’s Syndrome (DS) (2). Deficits in axonal transport also contribute to the pathogenesis of amyotrophic lateral sclerosis (ALS) (3,4), although the relationship with neurotrophin dynamics is not completely understood. Inherited peripheral neuropathies are also likely to be linked to alterations of axonal transport (5,6). A better understanding of the mechanisms by which axonal transport contributes to homeostatic control in neurons and how abnornalities of this process cause neuronal disfunction would provide cross-cutting benefits to many areas of human medicine, including neurodegeneration and infectious disease (7).
A major focus of our laboratory is to understand the machinery controlling sorting and long-range axonal transport in motor and sensory neurons. To extend our understanding of the regulation of axonal transport in vivo and its alteration during disease, we have established an intravital assay that allows us to monitor retrograde transport in the intact sciatic nerve (4,8). This assay permits the quantitative analysis of physiological axonal transport during disease progression in both sensory and motor neurons and is allowing us to study the effects of pharmacological interventions on this process (9).
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- Sleigh, et al. Proc Natl Acad Sci USA 114, E3324-E3333 (2017)
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- Gibbs et al J Neurosci Meth 257, 26-33 (2015)
- Gibbs et al Cell Death Dis 9, 596 (2018)
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