title: Understanding Dopaminergic Cell Death Pathways in Parkinson Disease.
abstract: Parkinson disease (PD) is a multifactorial neurodegenerative disorder, the etiology of which remains largely unknown. Progressive impairment of voluntary motor control, which represents the primary clinical feature of the disease, is caused by a loss of midbrain substantia nigra dopamine (DA) neurons. We present here a synthetic overview of cell-autonomous mechanisms that are likely to participate in DA cell death in both sporadic and inherited forms of the disease. In particular, we describe how damage to vulnerable DA neurons may arise from cellular disturbances produced by protein misfolding and aggregation, disruption of autophagic catabolism, endoplasmic reticulum (ER) stress, mitochondrial dysfunction, or loss of calcium homeostasis. Where pertinent, we show how these mechanisms may mutually cooperate to promote neuronal death.
authors.affiliation: Inserm, U 1127, F-75013 Paris, France; CNRS, UMR 7225, F-75013 Paris, France; Sorbonne Universités, UPMC Univ Paris 06, UMRS 1127, F-75013 Paris, France; Institut du Cerveau et de la Moelle Epinière, ICM, F-75013 Paris, France.
authors.forename: Patrick P
authors.initials: PP
authors.lastname: Michel
authors.affiliation: Inserm, U 1127, F-75013 Paris, France; CNRS, UMR 7225, F-75013 Paris, France; Sorbonne Universités, UPMC Univ Paris 06, UMRS 1127, F-75013 Paris, France; Institut du Cerveau et de la Moelle Epinière, ICM, F-75013 Paris, France. Electronic address: etienne.hirsch@upmc.fr.
authors.forename: Etienne C
authors.initials: EC
authors.lastname: Hirsch
authors.affiliation: Inserm, U 1127, F-75013 Paris, France; CNRS, UMR 7225, F-75013 Paris, France; Sorbonne Universités, UPMC Univ Paris 06, UMRS 1127, F-75013 Paris, France; Institut du Cerveau et de la Moelle Epinière, ICM, F-75013 Paris, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Hunot
mesh_terms: D000818:Animals; D016923:Cell Death / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D010300:Parkinson Disease / Q000378:metabolism*; D013378:Substantia Nigra / Q000378:metabolism
chemical_list: D004298:Dopamine