{"doi":"10.3390/biom10020216","title":"hNGF Peptides Elicit the NGF-TrkA Signalling Pathway in Cholinergic Neurons and Retain Full Neurotrophic Activity in the DRG Assay","abstract":"In the last decade, Nerve Growth Factor (NGF)-based clinical approaches have lacked specific and efficient Tyrosine Kinase A (TrkA) agonists for brain delivery. Nowadays, the characterization of novel small peptidomimetic is taking centre stage in preclinical studies, in order to overcome the main size-related limitation in brain delivery of NGF holoprotein for Central Nervous System (CNS) pathologies. Here we investigated the NGF mimetic properties of the human NGF 1-14 sequence (hNGF1-14) and its derivatives, by resorting to primary cholinergic and dorsal root ganglia (DRG) neurons. Briefly, we observed that: 1) hNGF1-14 peptides engage the NGF pathway through TrkA phosphorylation at tyrosine 490 (Y490), and activation of ShcC/PI3K and Plc-γ/MAPK signalling, promoting AKT-dependent survival and CREB-driven neuronal activity, as seen by levels of the immediate early gene c-Fos, of the cholinergic marker Choline Acetyltransferase (ChAT), and of Brain Derived Neurotrophic Factor (BDNF); 2) their NGF mimetic activity is lost upon selective TrkA inhibition by means of GW441756; 3) hNGF1-14 peptides are able to sustain DRG survival and differentiation in absence of NGF. Furthermore, the acetylated derivative Ac-hNGF1-14 demonstrated an optimal NGF mimetic activity in both neuronal paradigms and an electrophysiological profile similar to NGF in cholinergic neurons. Cumulatively, the findings here reported pinpoint the hNGF1-14 peptide, and in particular its acetylated derivative, as novel, specific and low molecular weight TrkA specific agonists in both CNS and PNS primary neurons.","journal":"Biomolecules","year":2020,"id":71422,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":17,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9588,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":377259,"name":"Elena Fico","orcid":"0000-0003-1730-277X","position":1,"is_corresponding":false},{"id":377260,"name":"Valentina Sposato","orcid":"0000-0001-8081-0692","position":2,"is_corresponding":false},{"id":377261,"name":"Silvia Caioli","orcid":"0000-0002-7888-0664","position":3,"is_corresponding":false},{"id":377971,"name":"Maria Teresa Ciotti","orcid":null,"position":4,"is_corresponding":false},{"id":377262,"name":"Cristina Zona","orcid":"0000-0002-3036-4839","position":5,"is_corresponding":false},{"id":377263,"name":"Delio Mercanti","orcid":"0000-0001-8301-2098","position":6,"is_corresponding":false},{"id":377264,"name":"Diego La Mendola","orcid":"0000-0002-4193-7612","position":7,"is_corresponding":false},{"id":377265,"name":"Cristina Satriano","orcid":"0000-0001-5348-5863","position":8,"is_corresponding":false},{"id":377266,"name":"Enrico Rizzarelli","orcid":"0000-0001-5367-0823","position":9,"is_corresponding":false},{"id":377267,"name":"Paola Tirassa","orcid":"0000-0002-8791-4424","position":10,"is_corresponding":false},{"id":377972,"name":"Pietro Calissano","orcid":null,"position":11,"is_corresponding":false},{"id":377258,"name":"Viviana Triaca","orcid":"0000-0001-8290-7279","position":0,"is_corresponding":true}],"reference_count":82,"raw_metadata":null,"created_at":"2026-07-18T21:43:57.004133Z","pmid":"32024191","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}