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The NGF Metabolic Pathway: New Opportunities for Biomarker Research and Drug Target Discovery

NGF Pathway Biomarkers and Drug Targets

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Recent Advances in NGF and Related Molecules

Part of the book series: Advances in Experimental Medicine and Biology ((CNNCSN,volume 1331))

Abstract

Recent research has demonstrated that degeneration of the basal forebrain cholinergic system, far from being a mere downstream mediator of Alzheimer’s disease (AD) symptoms, may play a disease-aggravating role in the continuum of AD pathology. The search for novel biomarkers of the cholinergic deficit in AD and novel therapeutic targets for the sustenance of the basal forebrain cholinergic system has therefore taken on more urgency. A novel model that explains the preferential vulnerability of basal forebrain cholinergic neurons in AD as the result of pathological alterations to nerve growth factor (NGF) metabolism offers an integrated investigative platform for the development of such biomarkers and therapeutics. By positing a reciprocal trophic interaction between the basal forebrain and its target tissues, this model can also explain the disease-modifying nature of the cholinergic deficit in AD and can incorporate other key factors in basal forebrain cholinergic degeneration, including NGF receptor changes and retrograde transport deficits in AD. This chapter will focus on the potential of NGF metabolic pathway biomarkers in AD as well as therapeutic targets to correct NGF metabolic deficits, aiding the development of novel pro-cholinergic therapeutics.

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Acknowledgements

The authors wish to thank and dedicate this chapter to Professor A. Claudio Cuello, for his continued mentorship and support and for sharing with us Rita Levi Montalcini’s inspirational legacy. Rowan Pentz is the recipient of a Returning Student Fellowship from the McGill Integrated Program in Neuroscience and CIHR Doctoral Award no. 201610GSD-385496-2466860. M. Florencia Iulita would like to acknowledge financial support from a Postdoctoral Research Fellowship from the Jérôme Lejeune and Sisley D’Ornano Foundations and from a pilot exploratory grant (no. 1941) from the Jérôme Lejeune Foundation.

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Authors and Affiliations

  1. Department of Neurology and Neurosurgery, McGill University, Montreal, Canada

    Rowan Pentz

  2. Sant Pau Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain

    M. Florencia Iulita

  3. Center of Biomedical Investigation Network for Neurodegenerative Diseases (CIBERNED), Madrid, Spain

    M. Florencia Iulita

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  1. Rowan Pentz
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  2. M. Florencia Iulita
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Correspondence to M. Florencia Iulita .

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  1. University of Bologna, Ozzano dell’Emilia, Bologna, Italy

    Laura Calzà

  2. IRET Foundation, Ozzano dell’Emilia, Bologna, Italy

    Luigi Aloe

  3. University of Bologna, Ozzano dell’Emilia, Bologna, Italy

    Luciana Giardino

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Pentz, R., Iulita, M.F. (2021). The NGF Metabolic Pathway: New Opportunities for Biomarker Research and Drug Target Discovery. In: Calzà, L., Aloe, L., Giardino, L. (eds) Recent Advances in NGF and Related Molecules. Advances in Experimental Medicine and Biology(), vol 1331. Springer, Cham. https://doi.org/10.1007/978-3-030-74046-7_4

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