Multiple sclerosis: Lessons from molecular neuropathology

  title={Multiple sclerosis: Lessons from molecular neuropathology},
  author={Hans Lassmann},
  journal={Experimental Neurology},
  • H. Lassmann
  • Published 1 December 2014
  • Biology, Psychology
  • Experimental Neurology
Chronic Demyelination and Axonal Degeneration in Multiple Sclerosis: Pathogenesis and Therapeutic Implications
The development of therapies to restore lost myelin and protect neurons is a promising avenue of investigation for the benefit of patients with MS.
Mechanisms of Neurodegeneration and Axonal Dysfunction in Progressive Multiple Sclerosis
The gradual accumulation of disability characteristic of the disease seems to also result from a different set of mechanisms, including in particular immune reactions confined to the Central Nervous System, which could act in combination.
Altered astrocytic function in experimental neuroinflammation and multiple sclerosis
This review will address the present knowledge that exists regarding the role of astrocytes in MS and experimental animal models of the disease, and suggest that disease progression and disability are better correlated with the maintenance of a persistent low‐grade inflammation inside the CNS, driven by local glial cells, like astroCytes and microglia.
Neuroprotective therapies for multiple sclerosis and other demyelinating diseases
  • P. Villoslada
  • Biology, Medicine
    Multiple Sclerosis and Demyelinating Disorders
  • 2016
Improvement in the understanding of underlying biology, in the design of clinical trials specific for assessing neuroprotection, and new technologies for developing novel therapies for neuroprotection suggest a new avenue for treating MS, Optic Neuritis or Neuromyelitis Optica.
A basic overview of multiple sclerosis immunopathology
To limit inflammatory demyelinating processes and delay disease progression, intervention to control inflammation must begin as early as possible.
The link of inflammation and neurodegeneration in progressive multiple sclerosis
Current data and recent hypothesis about pathological forces that drive progression of damage in MS, i.e. cumulative cortical demyelination and neurodegeneration as well as diffuse alterations throughout white and grey matter in the brain and spinal cord are summarized.
Newly Identified Deficiencies in the Multiple Sclerosis Central Nervous System and Their Impact on the Remyelination Failure
Results have led to a critical reassessment of MS pathogenesis, partly because EGF has little or no role in immunology, and other non-immunological MS abnormalities are reviewed.
Novel mechanism and biomarker of chronic progressive multiple sclerosis
The mechanisms proposed in the pathogenesis of SP‐MS are summarized, and a new pathogenic mechanism for neurodegeneration mediated by unique cytotoxic helper T cells is proposed.
Interactions between Axon Cytoskeleton Proteins and Oligodendrocytes during Remyelination
Four main factors might be involved in the repair defect in MS: I) astrocytic gliosis, II) axon degeneration, III) and/or OL alterations and finally the coexistence of these parameters with inflammatory cells and molecules in the lesions which renders the clarification of their respective involvement in the persistence of lesions difficult.


The astrocyte in multiple sclerosis revisited
It is proposed that the unequivocal selective early involvement of the astrocyte in MS lesions may have therapeutic relevance and multiple roles for this cell in the evolution of changes encountered in MS depending upon lesion stage and lesion topography.
Oxidative damage in multiple sclerosis lesions
The data suggest profound oxidative injury of oligodendrocytes and neurons to be associated with active demyelination and axonal or neuronal injury in multiple sclerosis.
Axonal damage in acute multiple sclerosis lesions.
The results show the expression of amyloid precursor protein in damaged axons within acute multiple sclerosis lesions, and in the active borders of less acute lesions, which may have implications for the design and timing of therapeutic intervention.
Heterogeneity of multiple sclerosis lesions: Implications for the pathogenesis of demyelination
At a given time point of the disease, the patterns of demyelination were heterogeneous between patients, but were homogenous within multiple active lesions from the same patient, suggesting that MS may be a disease with heterogeneous pathogenetic mechanisms.
Preferential Loss of Myelin‐Associated Glycoprotein Reflects Hypoxia‐Like White Matter Damage in Stroke and Inflammatory Brain Diseases
Brain white matter lesions presenting with MAG loss and apoptotic-like oligodendrocyte destruction, irrespective of their primary disease cause, revealed a prominent nuclear expression of hypoxia inducible factor-1α in various cell types, including oligodendedrocytes.
Inflammation induced by innate immunity in the central nervous system leads to primary astrocyte dysfunction followed by demyelination
It is shown here that damage of astrocytes and subsequent demyelination can also occur in the absence of autoantibody-mediated mechanisms, and suggest thatAstrocyte injury may be an important early step in the cascade of lesion formation in brain inflammation.
Lesion genesis in a subset of patients with multiple sclerosis: a role for innate immunity?
It is suggested that the areas of microglial activation represent an early stage of tissue injury, which precedes the formation of hypoxia-like demyelinated plaques in MS.
Cortical demyelination and diffuse white matter injury in multiple sclerosis.
Global brain pathology in multiple sclerosis is analysed, focusing on the normal-appearing white matter (NAWM) and the cortex, to suggest that multiple sclerosis starts as a focal inflammatory disease of the CNS, which gives rise to circumscribed demyelinated plaques in the white matter.
Neuromyelitis optica: a demyelinating disease characterized by acute destruction and regeneration of perivascular astrocytes
The findings raise the possibility that demyelination in MS may be a bystander effect of an astrocyte lesion, i.e. that MS is not a disease primarily of myelin and oligodendrocytes, and add to experimental evidence that the antibody is pathogenic.
Molecular Changes in White Matter Adjacent to an Active Demyelinating Lesion in Early Multiple Sclerosis
This study shows earliest molecular changes in white matter surrounding an actively demyelinating lesion during the first manifestation of MS, pointing toward a more widespread pathological process.