Damage to nuclear DNA in Lewy body disease.
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.
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Department of Neuropathology, Institute of Clinical Neurosciences, Frenchay Hospital, Bristol BS16 1LE, UK.
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
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