Ricerc@Sapienza

Alzheimer's disease is a devastating neurological illness with a high economic burden. The additional morbidity associated with social issues that arises along with the course of this disorder increases the need for a clear understanding of its etiopathogenesis thus allowing an implementation of novel pharmacological strategies. Despite astrocytes have been long described to actively participate in the regulation of brain circuits, available information is still poor. Even less information is available about their precise role in the pathogenesis of illness.

The Presenilin1 (PSEN1) gene encodes the catalytic peptide of the γ-secretase complex, a key enzyme that cleaves the amyloid-β protein precursor (AβPP), to generate the amyloid-β (Aβ) peptides, involved in Alzheimer’s Disease (AD). Other substrates of the γ-secretase, such as E-cadherin and Notch1, are involved in neurodevelopment and haematopoiesis. Gene-specific DNA methylation influences PSEN1 expression in AD animal models.

The nerve growth factor (NGF) belongs to a family of proteins termed neurotrophins, consisting of NGF, brain-derived neuro- trophic factor (BDNF), neurotrophin-3 (NT-3), NT-4/5 and NT-6. Today, NGF is well recognized to mediate a large number of trophobiological actions resulting in neurotrophic, immunotrophic and/or metabotrophic effects. The pathobiology of neurode- generative diseases, including Alzheimer disease, psychiatric disorders (e.g.