Neuroprotective strategies against neurodegeneration in cellular model systems

In the present study we analyzed new neuroprotective therapeutical strategies in PD (Parkinson’s disease) and AD (Alzheimer’s disease). Current therapeutic strategies for treating PD and AD offer mainly transient symptomatic relief but it is still impossible to block the loss of neuron and then the progression of PD and AD. There is considerable consensus that the increased production and/or aggregation of α- synuclein (α-syn) and β-amyloid peptide (Aβ), plays a central role in the pathogenesis of PD, related synucleinopathies and AD. Therefore, we identified antiamyloidogenic compounds and we tested their effect as neuroprotective drug-like molecules against α-syn and β-amyloid cytotoxicity in PC12. Herein, we show that two nitro-catechol compounds (entacapone and tolcapone) and 5 cathecol-containing compounds (dopamine, pyrogallol, gallic acid, caffeic acid and quercetin) with antioxidant and anti-inflammatory properties, are potent inhibitors of α-syn and β-amyloid oligomerization and fibrillization. Subsequently, we show that the inhibition of α-syn and β-amyloid oligomerization and fibrillization is correlated with the neuroprotection of these compounds against the α-syn and β-amyloid-induced cytotoxicity in PC12. Finally, we focused on the study of the neuroprotective role of microglia and on the possibility that the neuroprotection properties of these cells could be use as therapeutical strategy in PD and AD. Here, we have used an in vitro model to demonstrate neuroprotection of a 48 h-microglial conditioned medium (MCM) towards cerebellar granule neurons (CGNs) challenged with the neurotoxin 6-hydroxydopamine (6-OHDA), which induces a Parkinson-like neurodegeneration, with Aβ42, which induces a Alzheimer-like neurodegeneration, and glutamate, involved in the major neurodegenerative diseases. We show that MCM nearly completely protects CGNs from 6-OHDA neurotoxicity, partially from glutamate excitotoxicity but not from Aβ42 toxin.

Kinematics of the Sicily and Calabria Subduction System from Elastic Block Modeling of GPS Data

We use data from about 700 GPS stations in the EuroMediterranen region to investigate the present-day behavior of the the Calabrian subduction zone within the Mediterranean-scale plates kinematics and to perform local scale studies about the strain accumulation on active structures. We focus attenction on the Messina Straits and Crati Valley faults where GPS data show extentional velocity gradients of ∼3 mm/yr and ∼2 mm/yr, respectively. We use dislocation model and a non-linear constrained optimization algorithm to invert for fault geometric parameters and slip-rates and evaluate the associated uncertainties adopting a bootstrap approach. Our analysis suggest the presence of two partially locked normal faults. To investigate the impact of elastic strain contributes from other nearby active faults onto the observed velocity gradient we use a block modeling approach. Our models show that the inferred slip-rates on the two analyzed structures are strongly impacted by the assumed locking width of the Calabrian subduction thrust. In order to frame the observed local deformation features within the present- day central Mediterranean kinematics we realyze a statistical analysis testing the indipendent motion (w.r.t. the African and Eurasias plates) of the Adriatic, Cal- abrian and Sicilian blocks. Our preferred model confirms a microplate like behaviour for all the investigated blocks. Within these kinematic boundary conditions we fur- ther investigate the Calabrian Slab interface geometry using a combined approach of block modeling and χ2ν statistic. Almost no information is obtained using only the horizontal GPS velocities that prove to be a not sufficient dataset for a multi-parametric inversion approach. Trying to stronger constrain the slab geometry we estimate the predicted vertical velocities performing suites of forward models of elastic dislocations varying the fault locking depth. Comparison with the observed field suggest a maximum resolved locking depth of 25 km.