Multiple sclerosis as a neurodegenerative disease: pathology, mechanisms and therapeutic implications

Bakshi, 2008, MRI in multiple sclerosis: current status and future prospects, Lancet Neurol, 7, 615, 10.1016/S1474-4422(08)70137-6

De Stefano, 2001, Evidence of axonal damage in the early stages of multiple sclerosis and its relevance to disability, Arch Neurol, 58, 65, 10.1001/archneur.58.1.65

Aboul-Enein, 2010, Reduced NAA-levels in the NAWM of patients with MS is a feature of progression. A study with quantitative magnetic resonance spectroscopy at 3 Tesla, PLoS One, 5, e11625, 10.1371/journal.pone.0011625

Bjartmar, 2003, Axonal loss in the pathology of MS: consequences for understanding the progressive phase of the disease, J Neurol Sci, 206, 165, 10.1016/S0022-510X(02)00069-2

Losseff, 1996, Spinal cord atrophy and disability in multiple sclerosis. A new reproducible and sensitive MRI method with potential to monitor disease progression, Brain, 119, 701, 10.1093/brain/119.3.701

Pirko, 2011, Brain atrophy correlates with functional outcome in a murine model of multiple sclerosis, Neuroimage, 54, 802, 10.1016/j.neuroimage.2010.08.055

Lukas, 2010, Early central atrophy rate predicts 5 year clinical outcome in multiple sclerosis, J Neurol Neurosurg Psychiatry, 81, 1351, 10.1136/jnnp.2009.199968

Charil, 2007, Inflammatory demyelination and neurodegeneration in early multiple sclerosis, J Neurol Sci, 259, 7, 10.1016/j.jns.2006.08.017

Trapp, 2008, Multiple sclerosis: an immune or neurodegenerative disorder?, Annu Rev Neurosci, 31, 247, 10.1146/annurev.neuro.30.051606.094313

Frischer, 2009, The relation between inflammation and neurodegeneration in multiple sclerosis brains, Brain, 132, 1175, 10.1093/brain/awp070

Magliozzi, 2010, A gradient of neuronal loss and meningeal inflammation in multiple sclerosis, Ann Neurol, 68, 477, 10.1002/ana.22230

Androdias, 2010, Meningeal T cells associate with diffuse axonal loss in multiple sclerosis spinal cords, Ann Neurol, 68, 465, 10.1002/ana.22054

Mahad, 2008, Review: mitochondria and disease progression in multiple sclerosis, Neuropathol Appl Neurobiol, 34, 577, 10.1111/j.1365-2990.2008.00987.x

Witte, 2010, Mitochondrial dysfunction: a potential link between neuroinflammation and neurodegeneration?, Mitochondrion, 10, 411, 10.1016/j.mito.2010.05.014

Anderson, 2010, Abnormal tau phosphorylation in primary progressive multiple sclerosis, Acta Neuropathol, 119, 591, 10.1007/s00401-010-0671-4

Gunnarsson, 2011, Axonal damage in relapsing multiple sclerosis is markedly reduced by natalizumab, Ann Neurol, 69, 83, 10.1002/ana.22247

Sattler, 2010, Future neuroprotective strategies, Exp Neurol, 225, 40, 10.1016/j.expneurol.2009.08.016

Petratos, 2010, Novel therapeutic targets for axonal degeneration in multiple sclerosis, J Neuropathol Exp Neurol, 69, 323, 10.1097/NEN.0b013e3181d60ddb

Dutta, 2011, Mechanisms of neuronal dysfunction and degeneration in multiple sclerosis, Prog Neurobiol, 93, 1, 10.1016/j.pneurobio.2010.09.005

Rovaris, 2006, Secondary progressive multiple sclerosis: current knowledge and future challenges, Lancet Neurol, 5, 343, 10.1016/S1474-4422(06)70410-0

Confavreux, 2006, Natural history of multiple sclerosis: a unifying concept, Brain, 129, 606, 10.1093/brain/awl007

Confavreux, 2006, Age at disability milestones in multiple sclerosis, Brain, 129, 595, 10.1093/brain/awh714

Leray, 2010, Evidence for a two-stage disability progression in multiple sclerosis, Brain, 133, 1900, 10.1093/brain/awq076

Kutzelnigg, 2005, Cortical demyelination and diffuse white matter injury in multiple sclerosis, Brain, 128, 2705, 10.1093/brain/awh641

Siffrin, 2010, In vivo imaging of partially reversible TH17 cell-induced neuronal dysfunction in the course of encephalomyelitis, Immunity, 33, 424, 10.1016/j.immuni.2010.08.018

Howell, 2010, Activated microglia mediate axoglial disruption that contributes to axonal injury in multiple sclerosis, J Neuropathol Exp Neurol, 69, 1017, 10.1097/NEN.0b013e3181f3a5b1

Oksenberg, 2010, Multiple sclerosis genetics: is the glass half full, or half empty?, Nat Rev Neurol, 6, 429, 10.1038/nrneurol.2010.91

Graumann, 2003, Molecular changes in normal appearing white matter in multiple sclerosis are characteristic of neuroprotective mechanisms against hypoxic insult, Brain Pathol, 13, 554, 10.1111/j.1750-3639.2003.tb00485.x

Zeis, 2008, Normal-appearing white matter in multiple sclerosis is in a subtle balance between inflammation and neuroprotection, Brain, 131, 288, 10.1093/brain/awm291

Dutta, 2007, Activation of the ciliary neurotrophic factor (CNTF) signalling pathway in cortical neurons of multiple sclerosis patients, Brain, 130, 2566, 10.1093/brain/awm206

Ferguson, 1997, Axonal damage in acute multiple sclerosis lesions, Brain, 120, 393, 10.1093/brain/120.3.393

Petzold, 2008, Phosphorylation and compactness of neurofilaments in multiple sclerosis: indicators of axonal pathology, Exp Neurol, 213, 326, 10.1016/j.expneurol.2008.06.008

Schirmer, 2009, Substantial early, but nonprogressive neuronal loss in multiple sclerosis (MS) spinal cord, Ann Neurol, 66, 698, 10.1002/ana.21799

Schneider, 2004, Hyperphosphorylation and aggregation of tau in experimental autoimmune encephalomyelitis, J Biol Chem, 279, 55833, 10.1074/jbc.M409954200

Anderson, 2008, Abnormally phosphorylated tau is associated with neuronal and axonal loss in experimental autoimmune encephalomyelitis and multiple sclerosis, Brain, 131, 1736, 10.1093/brain/awn119

Anderson, 2009, Evidence for abnormal tau phosphorylation in early aggressive multiple sclerosis, Acta Neuropathol (Berl), 117, 583, 10.1007/s00401-009-0515-2

Li, 2006, Transient cognitive deficits are associated with the reversible accumulation of amyloid precursor protein after mild traumatic brain injury, Neurosci Lett, 409, 182, 10.1016/j.neulet.2006.09.054

Pesini, 1999, An immunohistochemical marker for Wallerian degeneration of fibers in the central and peripheral nervous system, Brain Res, 828, 41, 10.1016/S0006-8993(99)01283-4

Dziedzic, 2010, Wallerian degeneration: a major component of early axonal pathology in multiple sclerosis, Brain Pathol, 20, 976, 10.1111/j.1750-3639.2010.00401.x

Smith, 2002, The role of nitric oxide in multiple sclerosis, Lancet Neurol, 1, 232, 10.1016/S1474-4422(02)00102-3

Knoferle, 2010, Mechanisms of acute axonal degeneration in the optic nerve in vivo, Proc Natl Acad Sci U S A, 107, 6064, 10.1073/pnas.0909794107

Dutta, 2006, Mitochondrial dysfunction as a cause of axonal degeneration in multiple sclerosis patients, Ann Neurol, 59, 478, 10.1002/ana.20736

Mahad, 2008, Mitochondrial defects in acute multiple sclerosis lesions, Brain, 131, 1722, 10.1093/brain/awn105

Mahad, 2009, Mitochondrial changes within axons in multiple sclerosis, Brain, 132, 1161, 10.1093/brain/awp046

Kovacs, 2005, Neuropathology of white matter disease in Leber's hereditary optic neuropathy, Brain, 128, 35, 10.1093/brain/awh310

Kim, 2010, HDAC1 nuclear export induced by pathological conditions is essential for the onset of axonal damage, Nat Neurosci, 13, 180, 10.1038/nn.2471

Ciccarelli, 2010, Assessing neuronal metabolism in vivo by modeling imaging measures, J Neurosci, 30, 15030, 10.1523/JNEUROSCI.3330-10.2010

Ciccarelli, 2010, Spinal cord repair in MS: does mitochondrial metabolism play a role?, Neurology, 74, 721, 10.1212/WNL.0b013e3181d26968

Rossi, 2010, Abnormal activity of the Na/Ca exchanger enhances glutamate transmission in experimental autoimmune encephalomyelitis, Brain Behav Immun, 24, 1379, 10.1016/j.bbi.2010.07.241

Vercellino, 2007, Altered glutamate reuptake in relapsing-remitting and secondary progressive multiple sclerosis cortex: correlation with microglia infiltration, demyelination, and neuronal and synaptic damage, J Neuropathol Exp Neurol, 66, 732, 10.1097/nen.0b013e31812571b0

Wegner, 2006, Neocortical neuronal, synaptic, and glial loss in multiple sclerosis, Neurology, 67, 960, 10.1212/01.wnl.0000237551.26858.39

Centonze, 2009, Inflammation triggers synaptic alteration and degeneration in experimental autoimmune encephalomyelitis, J Neurosci, 29, 3442, 10.1523/JNEUROSCI.5804-08.2009

Ziehn, 2010, Hippocampal CA1 atrophy and synaptic loss during experimental autoimmune encephalomyelitis, EAE, Lab Invest, 90, 774, 10.1038/labinvest.2010.6

Dell'Acqua, 2010, Thalamocortical sensorimotor circuit in multiple sclerosis: an integrated structural and electrophysiological assessment, Hum Brain Mapp, 31, 1588, 10.1002/hbm.20961

Vergo, 2011, Acid-sensing ion channel 1 is involved in both axonal injury and demyelination in multiple sclerosis and its animal model, Brain, 134, 571, 10.1093/brain/awq337

Stirling, 2010, Mechanisms of axonal injury: internodal nanocomplexes and calcium deregulation, Trends Mol Med, 16, 160, 10.1016/j.molmed.2010.02.002

Shindler, 2010, Oral resveratrol reduces neuronal damage in a model of multiple sclerosis, J Neuroophthalmol, 30, 328, 10.1097/WNO.0b013e3181f7f833

Yang, 2010, Silencing Nogo-A promotes functional recovery in demyelinating disease, Ann Neurol, 67, 498, 10.1002/ana.21935

Jones, 2010, Improvement in disability after alemtuzumab treatment of multiple sclerosis is associated with neuroprotective autoimmunity, Brain, 133, 2232, 10.1093/brain/awq176

Papadopoulou, 2010, Dimethyl fumarate for multiple sclerosis, Expert Opin Investig Drugs, 19, 1603, 10.1517/13543784.2010.534778

Wilms, 2010, Dimethylfumarate inhibits microglial and astrocytic inflammation by suppressing the synthesis of nitric oxide, IL-1beta, TNF-alpha and IL-6 in an in-vitro model of brain inflammation, J Neuroinflammation, 7, 30, 10.1186/1742-2094-7-30

Fancy, 2010, Overcoming remyelination failure in multiple sclerosis and other myelin disorders, Exp Neurol, 225, 18, 10.1016/j.expneurol.2009.12.020