title: Damage to nuclear DNA in Lewy body disease.
abstract: To assess the significance of damaged nuclear DNA in autopsy brain tissue in Lewy body disease (LBD), we examined the patterns of expression of two DNA repair enzymes (PARP and DNA-PKCS), TUNEL and caspase-3 activation, in sections of midbrain and frontal cortex from nine patients with LBD who had not received L-DOPA, and from five neurologically normal controls. In LBD but not controls, many neurons and glia in the midbrain had translocated DNA-PKCS and PARP from the cytoplasm into the nucleus, particularly in the substantia nigra. LBD midbrains contained sparse TUNEL-positive neurons. Caspase-3 activity was largely restricted to microglia but was detected in an occasional nigral neuron. Nuclear DNA damage occurs in vivo in LBD but only rarely indicates neuronal apoptosis.
authors.affiliation: Department of Neuropathology, Institute of Clinical Neurosciences, Frenchay Hospital, Bristol BS16 1LE, UK.
authors.forename: S
authors.initials: S
authors.lastname: Love
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000032:analysis / Q000096:biosynthesis; D002452:Cell Count; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology*; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins; D005625:Frontal Lobe / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D020961:Lewy Body Disease / Q000378:metabolism / Q000473:pathology*; D008636:Mesencephalon / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins; D011065:Poly(ADP-ribose) Polymerases / Q000032:analysis / Q000096:biosynthesis; D017346:Protein Serine-Threonine Kinases / Q000032:analysis / Q000096:biosynthesis; D021122:Protein Subunits; D013378:Substantia Nigra / Q000378:metabolism / Q000473:pathology
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D021122:Protein Subunits; D004247:DNA; D011065:Poly(ADP-ribose) Polymerases; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; D017346:Protein Serine-Threonine Kinases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases