title: Canine degenerative myelopathy: a model of human amyotrophic lateral sclerosis.
abstract: Canine degenerative myelopathy (CDM) represents a unique naturally occurring animal model for human amyotrophic lateral sclerosis (ALS) because of similar clinical signs, neuropathologic findings, and involvement of the superoxide dismutase 1 (SOD1) mutation. A definitive diagnosis can only be made postmortem through microscopic detection of axonal degeneration, demyelination and astroglial proliferation, which is more severe in the dorsal columns of the thoracic spinal cord and in the dorsal portion of the lateral funiculus. Interestingly, the muscle acetylcholine receptor complexes are intact in CDM prior to functional impairment, thus suggesting that muscle atrophy in CDM does not result from physical denervation. Moreover, since sensory involvement seems to play an important role in CDM progression, a more careful investigation of the sensory pathology in ALS is also warranted. The importance of SOD1 expression remains unclear, while oxidative stress and denatured ubiquinated proteins appear to play a crucial role in the pathogenesis of CDM. In this updated narrative review we performed a systematic search of the published studies on CDM that may shed light on the pathophysiological mechanisms of human ALS. A better understanding of the factors that determine the disease progression in CDM may be beneficial for the development of effective treatments for ALS.
authors.affiliation: Department of Neurology, Christian Doppler Klinik, Paracelsus Medical University and Center for Cognitive Neuroscience, Ignaz-Harrer-Straße 79, A-5020 Salzburg, Austria; Department of Neurology, Franz Tappeiner Hospital, Via Rossini, 5, I-39012, Merano, Italy; Spinal Cord Injury and Tissue Regeneration Center, Paracelsus Medical University, Strubergasse 21, A-5020 Salzburg, Austria. Electronic address: raffaele.nardone@asbmeran-o.it.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Nardone
authors.affiliation: Department of Neurology, Christian Doppler Klinik, Paracelsus Medical University and Center for Cognitive Neuroscience, Ignaz-Harrer-Straße 79, A-5020 Salzburg, Austria; Spinal Cord Injury and Tissue Regeneration Center, Paracelsus Medical University, Strubergasse 21, A-5020 Salzburg, Austria.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Höller
authors.affiliation: Department of Neurology, Christian Doppler Klinik, Paracelsus Medical University and Center for Cognitive Neuroscience, Ignaz-Harrer-Straße 79, A-5020 Salzburg, Austria; Spinal Cord Injury and Tissue Regeneration Center, Paracelsus Medical University, Strubergasse 21, A-5020 Salzburg, Austria.
authors.forename: Alexandra C
authors.initials: AC
authors.lastname: Taylor
authors.affiliation: Department of Neurology, Franz Tappeiner Hospital, Via Rossini, 5, I-39012, Merano, Italy.
authors.forename: Piergiorgio
authors.initials: P
authors.lastname: Lochner
authors.affiliation: Department of Neurology, Franz Tappeiner Hospital, Via Rossini, 5, I-39012, Merano, Italy.
authors.forename: Frediano
authors.initials: F
authors.lastname: Tezzon
authors.affiliation: Department of Neurology, Christian Doppler Klinik, Paracelsus Medical University and Center for Cognitive Neuroscience, Ignaz-Harrer-Straße 79, A-5020 Salzburg, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Golaszewski
authors.affiliation: Department of Neurology, Franz Tappeiner Hospital, Via Rossini, 5, I-39012, Merano, Italy; Department of Neurological and Movement Sciences, Section of Clinical Neurology, University of Verona, Piazzale L.A. Scuro, I-37134 Verona, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Brigo
authors.affiliation: Department of Neurology, Christian Doppler Klinik, Paracelsus Medical University and Center for Cognitive Neuroscience, Ignaz-Harrer-Straße 79, A-5020 Salzburg, Austria; Spinal Cord Injury and Tissue Regeneration Center, Paracelsus Medical University, Strubergasse 21, A-5020 Salzburg, Austria.
authors.forename: Eugen
authors.initials: E
authors.lastname: Trinka
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000175:diagnosis / Q000209:etiology* / Q000235:genetics / Q000473:pathology*; D000818:Animals; D004195:Disease Models, Animal; D004285:Dogs; D006801:Humans; D013116:Spinal Cord / Q000473:pathology; D013118:Spinal Cord Diseases / Q000235:genetics / Q000473:pathology / Q000662:veterinary; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000072105:Superoxide Dismutase-1
chemical_list: C000606290:SOD1 protein, human; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1
keywords: Amyotrophic lateral sclerosis; Canine degenerative myelopathy; Muscle atrophy; Spinal cord; Superoxide dismutase 1 mutation