title: Selective neuronal vulnerability in Parkinson disease.
abstract: Intracellular α-synuclein (α-syn)-rich protein aggregates called Lewy pathology (LP) and neuronal death are commonly found in the brains of patients with clinical Parkinson disease (cPD). It is widely believed that LP appears early in the disease and spreads in synaptically coupled brain networks, driving neuronal dysfunction and death. However, post-mortem analysis of human brains and connectome-mapping studies show that the pattern of LP in cPD is not consistent with this simple model, arguing that, if LP propagates in cPD, it must be gated by cell- or region-autonomous mechanisms. Moreover, the correlation between LP and neuronal death is weak. In this Review, we briefly discuss the evidence for and against the spreading LP model, as well as evidence that cell-autonomous factors govern both α-syn pathology and neuronal death.
authors.affiliation: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
authors.forename: D James
authors.initials: DJ
authors.lastname: Surmeier
authors.affiliation: Centro Integral de Neurociencias A.C. (CINAC), HM Puerta del Sur, Hospitales de Madrid, Mostoles and CEU San Pablo University, 28938 Madrid, Spain.|Network Center for Biomedical Research on Neurodegenerative Diseases (CIBERNED), Instituto Carlos III, 28031 Madrid, Spain.
authors.forename: José A
authors.initials: JA
authors.lastname: Obeso
authors.affiliation: Brain and Mind Centre, Sydney Medical School, The University of Sydney, Sydney 2006, Australia.|School of Medical Sciences, University of New South Wales and Neuroscience Research Australia, Sydney 2052, Australia.
authors.forename: Glenda M
authors.initials: GM
authors.lastname: Halliday
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D016923:Cell Death; D006801:Humans; D016631:Lewy Bodies / Q000473:pathology*; D009474:Neurons / Q000473:pathology*; D010300:Parkinson Disease / Q000473:pathology*; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D051844:alpha-Synuclein