The effects of painless nerve growth factor on human microglia polarization

Lucia Lisi, Silvia Marinelli, Gabriella Maria Pia Ciotti, Michela Pizzoferrato, Federica Palmerio, Marta Chiavari, Antonino Cattaneo, Pierluigi Navarra*

*Autore corrispondente per questo lavoro

Risultato della ricerca: Contributo in rivistaArticolo in rivista


Previous studies in the rat suggest that microglial cells represent a potential druggable target for nerve growth factor (NGF) in the brain. The painless human Nerve Growth Factor (hNGFp) is a recombinant mutated form of human nerve growth factor (hNGF) that shows identical neurotrophic and neuroprotective properties of wild-type NGF but displays at least 10-fold lower algogenic activity. From the pharmacological point of view, hNGFp is a biased tropomyosin receptor kinase A (TrkA) agonist and displays a significantly lower affinity for the p75 neurotrophin receptor (p75NTR). This study aimed to evaluate the expression of TrkA and p75NTR NGF receptors in two different human microglia cell lines, and to investigate the effects of hNGFp and wild-type NGF (NGF) on L-arginine metabolism, taken as a marker of microglia polarization. Both NGF receptors are expressed in human microglia cell lines and are effective in transducing signals triggered by NGF and hNGFp. The latter and, to a lesser extent, NGF inhibit cytokine-stimulated inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production in these cells. Conversely NGF but not hNGFp stimulates arginase-mediated urea production.
Lingua originaleEnglish
pagine (da-a)969058-969068
Numero di pagine11
RivistaFrontiers in Cellular Neuroscience
Stato di pubblicazionePubblicato - 2022


  • NGF (nerve growth factor)
  • TrkA (tropomyosin receptor kinase)
  • microglia
  • p75NTR
  • painless NGF


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