title: Defective axonal transport: A common pathological mechanism in inherited and acquired peripheral neuropathies.
abstract: Peripheral neuropathies are characterized by a progressive and length-dependent loss of peripheral nerve function. This can be caused either by genetic defects, classified as 'inherited peripheral neuropathies', or they can be acquired throughout life. In that case, the disease is caused by various insults such as toxins and mechanical injuries, or it can arise secondary to medical conditions such as metabolic disorders, nutritional deficiencies, inflammation and infections. Peripheral neuropathies are not only very heterogeneous in etiology, but also in their pathology and clinical presentation. A commonality amongst all peripheral neuropathies is that no pharmacological disease-modifying therapies currently exist that can reverse or cure these diseases. Moreover, the length-dependent nature of the disease, affecting the longest nerves at the most distal sites, suggests an important role for disturbances in axonal transport, directly or indirectly linked to alterations in the cytoskeleton. In this review, we will give a systematic overview of the main arguments for the involvement of axonal transport defects in both inherited and acquired peripheral neuropathies. In addition, we will discuss the possible therapeutic strategies that can potentially counteract these disturbances, as this particular pathway might be a promising strategy to find a cure. Since counteracting axonal transport defects could limit the axonal degeneration and could be a driving force for neuronal regeneration, the benefits might be twofold.
authors.affiliation: KU Leuven - University of Leuven, Department of Neurosciences, Experimental Neurology and Leuven Research Institute for Neuroscience and Disease (LIND), Leuven, Belgium; VIB - Center for Brain & Disease Research, Laboratory of Neurobiology, Leuven, Belgium.
authors.forename: Robert
authors.initials: R
authors.lastname: Prior
authors.affiliation: KU Leuven - University of Leuven, Department of Neurosciences, Experimental Neurology and Leuven Research Institute for Neuroscience and Disease (LIND), Leuven, Belgium; VIB - Center for Brain & Disease Research, Laboratory of Neurobiology, Leuven, Belgium.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Van Helleputte
authors.affiliation: KU Leuven - University of Leuven, Department of Neurosciences, Experimental Neurology and Leuven Research Institute for Neuroscience and Disease (LIND), Leuven, Belgium; VIB - Center for Brain & Disease Research, Laboratory of Neurobiology, Leuven, Belgium.
authors.forename: Veronick
authors.initials: V
authors.lastname: Benoy
authors.affiliation: KU Leuven - University of Leuven, Department of Neurosciences, Experimental Neurology and Leuven Research Institute for Neuroscience and Disease (LIND), Leuven, Belgium; VIB - Center for Brain & Disease Research, Laboratory of Neurobiology, Leuven, Belgium. Electronic address: ludo.vandenbosch@kuleuven.vib.be.
authors.forename: Ludo
authors.initials: L
authors.lastname: Van Den Bosch
mesh_terms: D000818:Animals; D001370:Axonal Transport / Q000502:physiology*; D001369:Axons / Q000473:pathology*; D006801:Humans; D010523:Peripheral Nervous System Diseases / Q000235:genetics / Q000473:pathology / Q000503:physiopathology
keywords: Axonopathy; Charcot-Marie-Tooth disease; Chemotherapy; Diabetes; Dying-back neuropathy; Histone deacetylase 6; Intracellular trafficking; Mitochondria