Activation of Microglial Poly(ADP-Ribose)-Polymerase-1 by Cholesterol Breakdown Products during Neuroinflammation

Activation of Microglial Poly(ADP-Ribose)-Polymerase-1 by Cholesterol Breakdown Products during Neuroinflammation: a Link between Demyelination and Neuronal Damage

Multiple sclerosis (MS) is a chronic demyelinating disease in which it has only recently been suggested that damage to neuronal structures plays a key role. Here, we uncovered a link between the release of lipid breakdown products, found in the brain and cerebrospinal fluid (CSF) of MS patients as well as in experimental autoimmune encephalomyelitis, and neuronal damage mediated by microglial a...

Microglial Activation, Proliferation, and Poly(ADP-Ribose) Polymerase-1 Promotes

Poly(ADP-ribose) polymerase-1 promotes microglial activation, proliferation, and matrix metalloproteinase-9-mediated neuron death.

Activated microglia contribute to cell death in ischemic and neurodegenerative disorders of the CNS. Microglial activation is regulated in part by NF-kappaB, and the nuclear enzyme poly(ADP-ribose) polymerase-1 (PARP-1) enhances NF-kappaB binding to DNA. In this study, the role of PARP-1 in microglia-mediated neurotoxicity was assessed using microglia from wild-type (wt) and PARP-1-/- mice. Cul...

P 115: Potential Therapeutic Targets Related to Neuroinflammation in Treatment and Prevention of Autism

Autism spectrum disorder (ASD) is a mental condition, present from early childhood, characterized by great difficulty in communicating and forming relationships with others and using language. In the last four decades many studies have shown that immune responses in different regions of brain play an important role in ASD pathogenicity. A conservative estimate based on the research suggests tha...

Neurological and Histological Consequences Induced by In Vivo Cerebral Oxidative Stress: Evidence for Beneficial Effects of SRT1720, a Sirtuin 1 Activator, and Sirtuin 1-Mediated Neuroprotective Effects of Poly(ADP-ribose) Polymerase Inhibition

Poly(ADP-ribose)polymerase and sirtuin 1 are both NAD(+)-dependent enzymes. In vitro oxidative stress activates poly(ADP-ribose)polymerase, decreases NAD(+) level, sirtuin 1 activity and finally leads to cell death. Poly(ADP-ribose)polymerase hyperactivation contributes to cell death. In addition, poly(ADP-ribose)polymerase inhibition restores NAD(+) level and sirtuin 1 activity in vitro. In vi...