The IXth workshop on Apoptosis in Biology and Medicine brought together top international scientists to discuss current knowledge and views on the mechanisms of neuroinflammation, on the role of neuroinflammation in the context of different neurodegenerative diseases (i.e., Alzheimer's disease (AD), Parkinson's disease (PD), prion disease, multiple sclerosis, and HIV-associated dementia) and on the potential approaches for future therapeutic strategies. Also, the venue provided a unique opportunity for stimulating discussions particularly for young scientists, postdocs and PhD students, who presented their results in the evening poster sessions. This and previous workshops were organized within the PhD program of the University of Calabria in collaboration with the Universities of Catanzaro and Roma Tor Vergata, and was held in Porto Pirgos in Parghelia (VV, Italy).

In the opening lecture, Stuart Lipton (La Jolla, USA) presented an overview on the role of inflammatory mediators such as nitric oxide (NO) and reactive oxygen species (ROS) in neurodegenerative diseases, and more recent data on posttranslational modifications such as S-nitrosylation, which can contribute to protein misfolding and the progression of neurodegenerative diseases. In the case of the protein–disulfide isomerase (PDI), S-nitrosylation inhibits the enzymatic activity leading to the accumulation of polyubiquitinated proteins. This activates the unfolded protein response, which contributes to neuronal cell injury and loss. The formation of S-nitrosylated PDI occurs in several human diseases, including AD and PD. Lipton then reviewed the molecular basis for the action of memantine in neurological diseases. These are mediated, at least in part, by overactivation of N-methyl-D-aspartate (NMDA)-type glutamate receptors, producing excessive Ca2+ influx through the receptor's associated ion channel and consequent free-radical formation. Memantine, like the second generation-derivatives NitroMemantines, block excessive activation of NMDA receptors via a mechanism of uncompetitive open-channel block with a rapid ‘off-rate’. This mechanism affords blockade of the NMDA receptor during excessive activity without disrupting normal activity. In the case of Nitromemantines, the neuroprotective efficacy is enhanced by coupling NO to Memantine to target the thiol groups on the redox modulatory site(s) of the NMDA receptor. In contrast to PDI, S-nitrosylation of the NMDA receptor decreases its excessive activity and results in neuroprotection.

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