title: The BCL2 code to dopaminergic development and Parkinson's disease.
abstract: Continuous, nonrandom cell death during development of the dopaminergic system is carefully orchestrated by locally secreted growth factors and the expression of transcription factors to ensure every neuron is carefully placed in its appropriate position and no 'miswiring' occurs. We hypothesize that the machinery directly responsible for executing cell death is composed of a precisely calibrated array of BCL2 proteins. Paradoxically, these BCL2 proteins, required for proper development of the dopaminergic system, may also cause vulnerability of this system in the adult, as these BCL2 proteins have recently been linked to Parkinson's disease. In addition to the intriguing possibility of finding useful biomarkers for predicting later neurodegeneration, further investigation of these factors could open new paths for treating Parkinson's disease.
authors.affiliation: Swammerdam Institute of Life Sciences, University of Amsterdam, Postbus 94232/1090 GE, Amsterdam, The Netherlands. L.P.vanderheide@Uva.nl
authors.forename: Lars P
authors.initials: LP
authors.lastname: van der Heide
authors.forename: Marten P
authors.initials: MP
authors.lastname: Smidt
mesh_terms: D000328:Adult; D000818:Animals; D016923:Cell Death; D004298:Dopamine / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D028361:Mitochondrial Diseases / Q000235:genetics; D009474:Neurons / Q000378:metabolism; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2 / Q000235:genetics / Q000378:metabolism; D010300:Parkinson Disease / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D013378:Substantia Nigra / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D018398:Homeodomain Proteins; C539882:NR4A2 protein, human; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D019253:Proto-Oncogene Proteins c-bcl-2; D014157:Transcription Factors; C433629:homeobox protein PITX3; D004298:Dopamine