[Recent neuropathology of parkinsonian syndromes].
The understanding of the molecular mechanisms underlying Parkinson's disease, progressive supranuclear palsy, and multiple system atrophy has made significant progress in the recent years. Lewy body appears to be principally made of alpha-synuclein, a presynaptic protein. It also contains ubiquitin and some components of the proteasome: this suggests that alteration of protein catabolism may be involved in its formation. In favor of this hypothesis, it should be noted that Parkin, a protein that is mutated in autosomal recessive Parkinson disease, is a ubiquitin ligase. Immunohistochemistry has shown that alpha-synuclein accumulates not only in the cell body of the neurones (Lewy body) but also in their processes (Lewy neurites); it has emphasized the severity of the pathology in the nucleus basalis of Meynert, amygdala, CA2-3 sector of the hippocampus and cerebral cortex. Cortical Lewy bodies are not considered any more the marker of dementia with Lewy bodies: they are, indeed, found in true Parkinson disease cases. In progressive supranuclear palsy, 4 repeats tau accumulates in the cytoplasm of neurones and glia. At electron microscopy, the accumulation is made of straight filaments. It involves not only the neurones (where it is the main constituent of the neurofibrillary tangles) but also the glia. Astrocytic tuft is to day considered the morphological marker of progressive supranuclear palsy. Tau protein accumulates in the cell body of the oligodendrocyte as a "coiled body"; the protein is also integrated in the myelin sheath, when the cytoplasm of the oligodendrocyte wraps around the axon. This explains the numerous "threads" that are visible in cases of progressive supranuclear palsy. Striato-nigral degeneration, sporadic olivo-ponto-cerebellar atrophy and primitive orthostatic hypotension are various clinico-pathologic aspects of the same disorder: multiple system atrophy. It is also characterized by a morphological marker: the accumulation of alpha-synuclein in the cytoplasm of glial cells, particularly oligodendrocytes. The term synucleinopathy has been proposed to describe both idiopathic Parkinson disease and multiple system atrophy. The reason explaining the cellular topography of alpha-synuclein accumulation, neuronal in Parkinson disease, glial in multiple system atrophy is still unknown.
Duyckaerts
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C
Laboratoire de Neuropathologie Raymond Escourolle, Hôpital de La Salpêtrière, Paris.
Verny
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Hauw
J-J
JJ
D000679:Amygdala / Q000378:metabolism / Q000473:pathology; D001369:Axons / Q000378:metabolism / Q000473:pathology; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology; D003546:Cysteine Endopeptidases / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007024:Hypotension, Orthostatic / Q000150:complications; D007150:Immunohistochemistry; D016631:Lewy Bodies / Q000378:metabolism / Q000473:pathology; D008025:Ligases / Q000378:metabolism; D009097:Multienzyme Complexes / Q000378:metabolism; D019578:Multiple System Atrophy / Q000150:complications / Q000473:pathology; D009186:Myelin Sheath / Q000378:metabolism / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D009836:Oligodendroglia / Q000378:metabolism; D009849:Olivopontocerebellar Atrophies / Q000473:pathology; D020734:Parkinsonian Disorders / Q000150:complications / Q000378:metabolism* / Q000473:pathology*; D017729:Presynaptic Terminals / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D013494:Supranuclear Palsy, Progressive / Q000378:metabolism / Q000473:pathology; D051843:Synucleins; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases; D051844:alpha-Synuclein; D016875:tau Proteins / Q000378:metabolism
D009097:Multienzyme Complexes; D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; D025801:Ubiquitin; D051844:alpha-Synuclein; D016875:tau Proteins; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D008025:Ligases