Activation of PARP by Oxidative Stress Induced by beta-Amyloid: Implications for Alzheimer's Disease

作者：Abeti Rosella^*; Duchen Michael R

来源：Neurochemical Research, 2012, 37(11): 2589-2596.

DOI：10.1007/s11064-012-0895-x

• Alzheimer's disease
• beta-amyloid
• PARP-1
• Astrocytes
• Oxidative stress and mitochondria

Alzheimer's disease (AD) is a major neurodegenerative disease of old age, characterised by progressive cognitive impairment, dementia and atrophy of the central nervous system. The pathological hallmarks include the accumulation of the peptide beta-amyloid (A beta) which itself is toxic to neurons in culture. Recently, it has been discovered that A beta activates the protein poly(ADP-ribosyl) polymerase-1 (PARP-1) specifically in astrocytes, leading indirectly to neuronal cell death. PARP-1 is a DNA repair enzyme, normally activated by single strand breaks associated with oxidative stress, which catalyses the formation of poly ADP-ribose polymers from nicotinamide adenine dinucleotide (NAD(+)). The pathological over activation of PARP-1 causes depletion of NAD(+) and leads to cell death. Here we review the relationship between AD and PARP-1, and explore the role played by astrocytes in neuronal death. AD has so far proven refractory to any effective treatment. Identification of these pathways represents a step towards a greater understanding of the pathophysiology of this devastating disease with the potential to explore novel therapeutic targets.

• 出版日期2012-11