Biomaterial Database

Increased poly(ADP-ribosyl)ation of nuclear proteins in Alzheimer's disease. 1999

S Love, and R Barber, and G K Wilcock

Department of Neuropathology, Frenchay Hospital, Bristol, UK. seth.love@bris.ac.uk

Experimental studies indicate that overactivation of the DNA repair protein poly(ADP-ribose) polymerase (PARP) in response to oxidative damage to DNA can cause cell death due to depletion of NAD+. Oxidative damage to DNA and other macromolecules has been reported to be increased in the brains of patients with Alzheimer's disease. In the present study we sought evidence of PARP activation in Alzheimer's disease by immunostaining sections of frontal and temporal lobe from autopsy material of 20 patients and 10 controls, both for PARP itself and for its end-product, poly(ADP-ribose). All of the brains had previously been subjected to detailed neuropathological examination to confirm the diagnosis of Alzheimer's disease or, in the controls, to exclude Alzheimer's disease-type pathology. Double immunolabelling for poly(ADP-ribose) and microtubule-associated protein 2 (MAP2), glial fibrillary-acidic protein (GFAP), CD68, A beta-protein or tau was used to assess the identity of the cells with poly(ADP-ribose) accumulation and their relationship to plaques and neurofibrillary tangles. Both PARP- and poly(ADP-ribose)-immunolabelled cells were detected in a much higher proportion of Alzheimer's disease (20 out of 20) brains than of control brains (5 out of 10) (P = 0.0018). Double-immunolabelling for poly(ADP-ribose) and markers of neuronal, astrocytic and microglial differentiation (MAP2, GFAP and CD68, respectively) showed many of the cells containing poly(ADP-ribose) to be neurons. Most of these were small pyramidal neurons in cortical laminae 3 and 5. A few of the cells containing poly(ADP-ribose) were astrocytes. No poly(ADP-ribose) accumulation was detected in microglia. Double-immunolabelling for poly(ADP-ribose) and tau or A beta-protein indicated that the cells with accumulation of poly(ADP-ribose) did not contain tangles and relatively few occurred within plaques. Our findings indicate that there is enhanced PARP activity in Alzheimer's disease and suggest that pharmacological interventions aimed at inhibiting PARP may have a role in slowing the progression of the disease.

UI	MeSH Term	Description	Entries
D007124	Immunoenzyme Techniques	Immunologic techniques based on the use of: (1) enzyme-antibody conjugates; (2) enzyme-antigen conjugates; (3) antienzyme antibody followed by its homologous enzyme; or (4) enzyme-antienzyme complexes. These are used histologically for visualizing or labeling tissue specimens.	Antibody Enzyme Technique, Unlabeled,Enzyme Immunoassay,Enzyme-Labeled Antibody Technique,Immunoassay, Enzyme,Immunoperoxidase Techniques,Peroxidase-Antiperoxidase Complex Technique,Peroxidase-Labeled Antibody Technique,Antibody Enzyme Technic, Unlabeled,Enzyme-Labeled Antibody Technic,Immunoenzyme Technics,Immunoperoxidase Technics,Peroxidase-Antiperoxidase Complex Technic,Peroxidase-Labeled Antibody Technic,Antibody Technic, Enzyme-Labeled,Antibody Technic, Peroxidase-Labeled,Antibody Technics, Enzyme-Labeled,Antibody Technics, Peroxidase-Labeled,Antibody Technique, Enzyme-Labeled,Antibody Technique, Peroxidase-Labeled,Antibody Techniques, Enzyme-Labeled,Antibody Techniques, Peroxidase-Labeled,Enzyme Immunoassays,Enzyme Labeled Antibody Technic,Enzyme Labeled Antibody Technique,Enzyme-Labeled Antibody Technics,Enzyme-Labeled Antibody Techniques,Immunoassays, Enzyme,Immunoenzyme Technic,Immunoenzyme Technique,Immunoperoxidase Technic,Immunoperoxidase Technique,Peroxidase Antiperoxidase Complex Technic,Peroxidase Antiperoxidase Complex Technique,Peroxidase Labeled Antibody Technic,Peroxidase Labeled Antibody Technique,Peroxidase-Antiperoxidase Complex Technics,Peroxidase-Antiperoxidase Complex Techniques,Peroxidase-Labeled Antibody Technics,Peroxidase-Labeled Antibody Techniques,Technic, Enzyme-Labeled Antibody,Technic, Immunoenzyme,Technic, Immunoperoxidase,Technic, Peroxidase-Antiperoxidase Complex,Technic, Peroxidase-Labeled Antibody,Technics, Enzyme-Labeled Antibody,Technics, Immunoenzyme,Technics, Immunoperoxidase,Technics, Peroxidase-Antiperoxidase Complex,Technics, Peroxidase-Labeled Antibody,Technique, Enzyme-Labeled Antibody,Technique, Immunoenzyme,Technique, Immunoperoxidase,Technique, Peroxidase-Antiperoxidase Complex,Technique, Peroxidase-Labeled Antibody,Techniques, Enzyme-Labeled Antibody,Techniques, Immunoenzyme,Techniques, Immunoperoxidase,Techniques, Peroxidase-Antiperoxidase Complex,Techniques, Peroxidase-Labeled Antibody
D008297	Male		Males
D008869	Microtubule-Associated Proteins	High molecular weight proteins found in the MICROTUBULES of the cytoskeletal system. Under certain conditions they are required for TUBULIN assembly into the microtubules and stabilize the assembled microtubules.	Ensconsin,Epithelial MAP, 115 kDa,Epithelial Microtubule-Associate Protein, 115 kDa,MAP4,Microtubule Associated Protein,Microtubule Associated Protein 4,Microtubule Associated Protein 7,Microtubule-Associated Protein,Microtubule-Associated Protein 7,E-MAP-115,MAP1 Microtubule-Associated Protein,MAP2 Microtubule-Associated Protein,MAP3 Microtubule-Associated Protein,Microtubule Associated Proteins,Microtubule-Associated Protein 1,Microtubule-Associated Protein 2,Microtubule-Associated Protein 3,7, Microtubule-Associated Protein,Associated Protein, Microtubule,E MAP 115,Epithelial Microtubule Associate Protein, 115 kDa,MAP1 Microtubule Associated Protein,MAP2 Microtubule Associated Protein,MAP3 Microtubule Associated Protein,Microtubule Associated Protein 1,Microtubule Associated Protein 2,Microtubule Associated Protein 3,Microtubule-Associated Protein, MAP1,Microtubule-Associated Protein, MAP2,Microtubule-Associated Protein, MAP3,Protein 7, Microtubule-Associated,Protein, Microtubule Associated,Protein, Microtubule-Associated
D008875	Middle Aged	An adult aged 45 - 64 years.	Middle Age
D009474	Neurons	The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.	Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D009687	Nuclear Proteins	Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.	Nucleolar Protein,Nucleolar Proteins,Nuclear Protein,Protein, Nuclear,Protein, Nucleolar,Proteins, Nuclear,Proteins, Nucleolar
D011064	Poly Adenosine Diphosphate Ribose	A polynucleotide formed from the ADP-RIBOSE moiety of nicotinamide-adenine dinucleotide (NAD) by POLY(ADP-RIBOSE) POLYMERASES.	Poly ADP Ribose,Poly(ADP-Ribose),Poly-ADPR,Poly-Adenosine Diphosphate-Ribose,ADP Ribose, Poly,Diphosphate-Ribose, Poly-Adenosine,Poly ADPR,Ribose, Poly ADP
D011065	Poly(ADP-ribose) Polymerases	Enzymes that catalyze the transfer of multiple ADP-RIBOSE groups from nicotinamide-adenine dinucleotide (NAD) onto protein targets, thus building up a linear or branched homopolymer of repeating ADP-ribose units i.e., POLY ADENOSINE DIPHOSPHATE RIBOSE.	ADP-Ribosyltransferase (Polymerizing),Poly ADP Ribose Polymerase,Poly(ADP-Ribose) Synthase,Poly(ADP-ribose) Polymerase,PARP Polymerase,Poly ADP Ribose Transferase,Poly ADP-Ribose Synthase,Poly(ADP-Ribose) Transferase,Poly(ADPR) Polymerase,Poly(ADPribose) Polymerase,Poly ADP Ribose Synthase,Polymerase, PARP,Synthase, Poly ADP-Ribose
D001923	Brain Chemistry	Changes in the amounts of various chemicals (neurotransmitters, receptors, enzymes, and other metabolites) specific to the area of the central nervous system contained within the head. These are monitored over time, during sensory stimulation, or under different disease states.	Chemistry, Brain,Brain Chemistries,Chemistries, Brain
D005260	Female		Females