Next Article in Journal
Synthesis of Novel Arylhydrazones Bearing 8-Trifluoromethyl Quinoline: Crystal Insights, Larvicidal Activity, ADMET Predictions, and Molecular Docking Studies
Previous Article in Journal
Formulation and Characterization of Oxiconazole-Loaded Novasomes to Enhance the Treatment of Fungus Infections: Experimentally Induced Candidiasis in Rat
Previous Article in Special Issue
Nerve Growth Factor in Pediatric Brain Injury: From Bench to Bedside
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Pharmaceuticals
Volume 18
Issue 12
10.3390/ph18121805
pharmaceuticals-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Review

Nerve Growth Factor in Diabetes Mellitus: Pathophysiological Mechanisms, Biomarkers and Therapeutic Opportunities

by
Mattia Massimino
1,
Mariangela Rubino
1,
Maria Resilde Natale
1,
Luca Salerno
1,
Stefania Belviso
2,
Elettra Mancuso
3,
Annamaria Dagostino
1,
Davide Demasi
1,
Flora Barreca
1,
Carolina Averta
4,
Angela Palummo
1,
Gaia Chiara Mannino
1,* and
Francesco Andreozzi
1
1
Department of Medical and Surgical Science, University Magna Graecia of Catanzaro, Viale Europa, 88100 Catanzaro, Italy
2
Azienda Ospedaliera Universitaria “Renato Dulbecco” University Hospital of Catanzaro, 88100 Catanzaro, Italy
3
Department of Science of Health, University Magna Graecia of Catanzaro, Viale Europa, 88100 Catanzaro, Italy
4
Department of Experimental and Clinical Medicine, University Magna Graecia of Catanzaro, Viale Europa, 88100 Catanzaro, Italy
*
Author to whom correspondence should be addressed.
Pharmaceuticals 2025, 18(12), 1805; https://doi.org/10.3390/ph18121805
Submission received: 4 September 2025 / Revised: 10 November 2025 / Accepted: 20 November 2025 / Published: 26 November 2025
(This article belongs to the Special Issue Applications of Nerve Growth Factor in Pharmaceuticals)
Versions Notes

Abstract

Background: Type 2 diabetes mellitus represents a global health challenge, with chronic hyperglycemia leading to a spectrum of microvascular and macrovascular complications. This narrative review provides a comprehensive and integrated analysis of the nerve growth factor (NGF) axis as a key, yet underrecognized, pathogenic mechanism. Methods: This narrative review was conducted in accordance with scholarly standards for non-systematic syntheses (SANRA). We included both clinical and preclinical studies focusing on NGF/proNGF biology and interventions across major diabetes complications. Discussion: Growing evidence highlights NGF as a pivotal mediator at the crossroads of neuronal, vascular and metabolic pathways. In diabetes, a disrupted balance between mature NGF and its precursor proNGF, favors the detrimental p75NTR pathway, leading to increased cellular stress, inflammation and apoptosis. In this narrative review, we examine how a decline in mature NGF and a relative excess of proNGF contribute to the pathophysiology of diabetic complications across various organ systems. We highlight the dual role of the NGF axis: while NGF-TrkA signaling consistently confers neuroprotective and vasculoprotective benefits, unchecked proNGF-p75NTR activity amplifies tissue damage. Conclusions: Collectively, the evidence identifies NGF as a candidate biomarker for both early tissue distress and therapeutic monitoring. We conclude by outlining key priorities for future research, including the development of standardized assays and the initiation of well-designed clinical trials to translate these promising strategies for early detection and treatment of diabetes-related complications.
Keywords: type 2 diabetes mellitus; nerve growth factor; proNGF; biomarkers; therapeutic targets; diabetes complications; translational medicine type 2 diabetes mellitus; nerve growth factor; proNGF; biomarkers; therapeutic targets; diabetes complications; translational medicine

Share and Cite

MDPI and ACS Style

Massimino, M.; Rubino, M.; Natale, M.R.; Salerno, L.; Belviso, S.; Mancuso, E.; Dagostino, A.; Demasi, D.; Barreca, F.; Averta, C.; et al. Nerve Growth Factor in Diabetes Mellitus: Pathophysiological Mechanisms, Biomarkers and Therapeutic Opportunities. Pharmaceuticals 2025, 18, 1805. https://doi.org/10.3390/ph18121805

AMA Style

Massimino M, Rubino M, Natale MR, Salerno L, Belviso S, Mancuso E, Dagostino A, Demasi D, Barreca F, Averta C, et al. Nerve Growth Factor in Diabetes Mellitus: Pathophysiological Mechanisms, Biomarkers and Therapeutic Opportunities. Pharmaceuticals. 2025; 18(12):1805. https://doi.org/10.3390/ph18121805

Chicago/Turabian Style

Massimino, Mattia, Mariangela Rubino, Maria Resilde Natale, Luca Salerno, Stefania Belviso, Elettra Mancuso, Annamaria Dagostino, Davide Demasi, Flora Barreca, Carolina Averta, and et al. 2025. "Nerve Growth Factor in Diabetes Mellitus: Pathophysiological Mechanisms, Biomarkers and Therapeutic Opportunities" Pharmaceuticals 18, no. 12: 1805. https://doi.org/10.3390/ph18121805

APA Style

Massimino, M., Rubino, M., Natale, M. R., Salerno, L., Belviso, S., Mancuso, E., Dagostino, A., Demasi, D., Barreca, F., Averta, C., Palummo, A., Mannino, G. C., & Andreozzi, F. (2025). Nerve Growth Factor in Diabetes Mellitus: Pathophysiological Mechanisms, Biomarkers and Therapeutic Opportunities. Pharmaceuticals, 18(12), 1805. https://doi.org/10.3390/ph18121805

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop