• dendrimers
• microglia
• neurodegenerative disorders
• neuroinflammation

Last decades of research in the field of neurodegenerative disorders helped to clarify some
mechanisms underlying the pathophysiology of this class of diseases, putting in evidence the contribution of diverse factors. Between them, the microglia-mediated neuroinflammation process has emerged as key element at the basis of neuronal loss. Such process is due to a population of non-neuronal cells part of a distinct lineage of the innate immune system, restricted to the brain parenchyma and indispensable for the correct development and functioning of central nervous system. Their most important role is constantly patrolling the nearby regions to detect possible disturbing stimuli. When activated by an injury or harmful signals, microglia cells were able to trigger an inflammatory response, initially aimed at the removal of noxious elements, followed by a resolutive phase, to restore the damage and promote tissue healing.
The unbalance of this equilibrium, between neurotoxic and neuroprotective microglia, bring to a sustained inflammatory response, with devastating consequences for surrounding neurons.
Indeed, persistent microglia activation is commonly present like principal orchestrator of neuronal apoptosis process, characteristic of neurodegenerative disorders.
From these evidences emerged the role of microglia as possible target for neuroinflammation treatments in these class of pathologies.

Currently, promising candidates to treat neuroinflammation, are a class of synthetic designed molecules called dendrimers. They are nanosized particles of global shape, with a hyper-branched structure that extends from a central core. Due to their numerous properties and their great versatility, dendrimers are efficient nano tools, intensively explored for multiple biological applications.
Among the different classes of dendrimers, some categories display important intrinsic properties mainly as immunomodulator agents.
Part of the mentioned category is the AzaBisPhosphonate (ABP) dendrimer, a phosphorus containing nanoparticle that works as an anti-inflammatory drug. It is a ramified dendrimer with a size in the order of 3nm, that exposes phosphorus-based groups at the periphery. ABP dendrimer shows a clear anti-inflammatory activity on human monocytes and animal model of chronic inflammatory disorders. Its main effect rely on the prevention of the pro-inflammatory activation of monocytes cells, leading to an anti-inflammatory polarization that promote a protective phenotype.
To explore whether ABP is able to exert its intrinsic anti-inflammatory activity on microglia cells, we tested their efficiency as immunomodulator nanoparticle in diverse model of microglia cell lines and adult primary murine microglia.
Diverse experiments were conducted revealing their anti-inflammatory activity on microglia population that joint with previous observations, highlights ABP dendrimer as suitable candidate to target microglia-mediated neuroinflammation in neurodegenerative disorders.
However, results obtained until now on microglia cells, and collected in this experience, require further assessment to elucidate completely the ABP intrinsic properties.