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This pathology is associated with axonal degeneration of different degrees. The clinical manifestation is most commonly that of a mixed motor\u2013sensory peripheral axonopathy with a disto\u2010proximal pattern of progression, as in cases of chronic exposure to n\u2010hexane and carbon disulphide. It has been demonstrated that protein adduct formation is a primary molecular mechanism of toxicity in these axonopathies, but how this mechanism leads to neurofilament accumulation and axonal degeneration remains unclear. Furthermore, little is known regarding the mechanisms of neurofilamentous axonopathy caused by 3,3\u2032\u2010iminodipropionitrile, an experimental toxin that induces proximal axon swelling that is strikingly similar to that found in early amyotrophic lateral sclerosis. Here, we review the available data and main hypotheses regarding the toxic axonopathies and compare them with the current knowledge of the biological basis of neurofilament transport. We also review recent studies addressing the question of how these axonopathies may cause axonal degeneration. Understanding the mechanisms underlying the toxic axonopathies may provide insight into the relationship between neurofilament behaviour and axonal degeneration, hopefully enabling the identification of new targets for therapeutic intervention. Because neurofilament abnormalities are a common feature of many neurodegenerative diseases, advances in this area may have a wider impact beyond toxicological significance.<\/jats:p>","DOI":"10.1111\/joim.12030","type":"journal-article","created":{"date-parts":[[2013,4,12]],"date-time":"2013-04-12T10:03:54Z","timestamp":1365761034000},"page":"478-489","source":"Crossref","is-referenced-by-count":34,"title":["Toxic neurofilamentous axonopathies\u2013 accumulation of neurofilaments and axonal degeneration"],"prefix":"10.1111","volume":"273","author":[{"given":"J.","family":"Llorens","sequence":"first","affiliation":[{"name":"Departament de Ci\u00e8ncies Fisiol\u00f2giques II Universitat de Barcelona and Institut d'Investigaci\u00f3 Biom\u00e8dica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat Catalunya Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,4,22]]},"reference":[{"key":"e_1_2_11_2_1","volume-title":"Experimental and Clinical Neurotoxicology","author":"Spencer 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