title: Axonopathy in peripheral neuropathies: Mechanisms and therapeutic approaches for regeneration.
abstract: Peripheral neuropathies (PNs) are injuries or diseases of the nerves which arise from varied aetiology, including metabolic disease, trauma and drug toxicity. The clinical presentation depends on the type of neuropathy, and may include the loss of motor, sensory and autonomic functions, or development of debilitating neuropathic pain distal to the injury site. It can be challenging to identify the aetiology of PNs, as the clinical syndromes are often indistinct. However, the mechanisms that underlie pathological changes in peripheral neuropathy are fundamentally different, depending on the trigger. This review focuses on the axonopathy observed in two frequently encountered forms of peripheral neuropathy, diabetic neuropathy and chemotherapy-induced neuropathy. A key manifestation of axonopathy in PN is the degeneration of terminal arbors of peripheral nerves, resulting in a loss of epidermal nerve fibres and inappropriate termination of nerve endings. Many symptoms of PN arise from aberrant termination of nerve endings, and the underlying axonopathy may be non-reversible, as nerve regeneration after injury and disease is often poor, absent, or aberrant. Directed guidance of terminal arbors back into the epidermis is therefore a suggested approach to treat peripheral neuropathy. This review will outline potential strategies to enhance and guide axonal regeneration and reinnervation in the skin. Using diabetic neuropathy and chemotherapy-induced neuropathy as specific examples, this review examines the setbacks encountered with the translation of growth factors into therapeutics for human neuropathy, and suggests a number of approaches for topical drug delivery.
authors.affiliation: Wicking Dementia Research & Education Centre, TAS, Australia; School of Medicine, University of Tasmania, TAS, Australia. Electronic address: Lila.landowski@utas.edu.au.
authors.forename: Lila M
authors.initials: LM
authors.lastname: Landowski
authors.affiliation: Peripheral Nerve Laboratory, Mayo Clinic, MN, USA.
authors.forename: P James B
authors.initials: PJ
authors.lastname: Dyck
authors.affiliation: Peripheral Nerve Laboratory, Mayo Clinic, MN, USA.
authors.forename: JaNean
authors.initials: J
authors.lastname: Engelstad
authors.affiliation: Menzies Institute for Medical Research, TAS, Australia; Royal Hobart Hospital, TAS, Australia.
authors.forename: Bruce V
authors.initials: BV
authors.lastname: Taylor
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology*; D003929:Diabetic Neuropathies / Q000473:pathology / Q000628:therapy; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000627:therapeutic use; D009416:Nerve Regeneration; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000473:pathology* / Q000628:therapy*
chemical_list: D036341:Intercellular Signaling Peptides and Proteins
keywords: Axonopathy; Chemotherapy-induced neuropathy; Cisplatin; Diabetic neuropathy; Paclitaxel; Peripheral neuropathy