title: [Update on the pathophysiology of Parkinson' disease].
abstract: Changes in the substantia nigra of patients with Parkinson's disease were suspected by Brissaud in the late 19th century. They were subsequently confirmed by Tretiakoff but neglected by Lewy, who described the inclusion bodies that bear his name. The experimental Parkinsonian syndrome caused by reserpine led Carlsson to discover the neuromediatory role of dopamine, a finding at the origin of L-DOPA therapy. Identification of a mutation of the alpha-synuclein gene in cases of familial Parkinson's disease with autosomal dominant transmission was followed by the detection of the protein product in Lewy bodies and neurites. Alpha-synuclein is now recognized as being the main constituent of Lewy bodies. Alpha-synuclein immunohistochemistry has revealed that lesions can extend from the autonomous nervous system to the cortex (in Lewy body dementia). The Lewy body itself does not appear to be the direct cause of symptoms, which correlate better with neuronal death. Neuronal death could be due to metabolic disturbances related to alpha-synuclein accumulation, ubiquitin-proteasome system dysfunction, or oxidative stress. Non-autonomous cell death, caused by neuro-inflammation or gliosis, has also been incriminated.
authors: Laboratoire de neuropathologie Escourolle - Hôpital de la Pitié Salpêtrière - 47 bld de l'Hôpital, 75651 Paris cedex 13. charles.duyckaerts@psl.aphp.fr
authors: Charles
authors: C
authors: Duyckaerts
authors: Véronique
authors: V
authors: Sazdovitch
authors: Danielle
authors: D
authors: Seilhean
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D035843:Biomedical Research / Q000639:trends*; D004298:Dopamine / Q000235:genetics / Q000502:physiology / Q000627:therapeutic use; D006801:Humans; D016631:Lewy Bodies / Q000378:metabolism / Q000473:pathology; D009154:Mutation / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D010300:Parkinson Disease / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D013378:Substantia Nigra / Q000378:metabolism / Q000473:pathology; D051844:alpha-Synuclein / Q000235:genetics / Q000502:physiology
chemical_list: D009419:Nerve Tissue Proteins; D051844:alpha-Synuclein; D004298:Dopamine