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Rita Levi-Montalcini, NGF Metabolism in Health and in the Alzheimer’s Pathology

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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

This chapter relates biographic personal and scientific interactions with Rita Levi-Montalcini. It highlights research from our laboratory inspired by Rita’s fundamental discovery. This work from studies on potentially neuro-reparative gangliosides, their interactions with NGF, the role of exogenous NGF in the recovery of degenerating cholinergic neurons of the basal forebrain to the evidence that endogenous NGF maintains the “day-to-day” cortical synaptic phenotype and the discovery of a novel CNS “NGF metabolic pathway.” This brain pathway’s conceptual platform allowed the investigation of its status during the Alzheimer’s disease (AD) pathology. This revealed a major compromise of the conversion of the NGF precursor molecule (proNGF) into the most biologically active molecule, mature NGF (mNGF). Furthermore, in this pathology, we found enhanced protein levels and enzymatic activity of the proteases responsible for the proteolytic degradation of mNGF. A biochemical prospect explaining the tropic factor vulnerability of the NGF-dependent basal forebrain cholinergic neurons and of their synaptic terminals. The NGF deregulation of this metabolic pathway is evident at preclinical stages and reflected in body fluid particularly in the cerebrospinal fluid (CSF). The findings of a deregulation of the NGF metabolic pathway and its reflection in plasma and CSF are opening doors for the development of novel biomarkers for preclinical detection of AD pathology both in Alzheimer’s and in Down syndrome (DS) with “silent” AD pathology.

My life has been enriched by excellent human relations, work, and interests. I have never felt lonely.

Rita Levi-Montalcini

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Acknowledgments

The work narrated above was made historically possible by several UK, Canada, and US research-granting institutions, notably the UK MRC and Wellcome Trust, from Canada the MRC, CIHR, and the Alzheimer Society of Canada, and from the United States the Alzheimer Association and the NIH. Most importantly, the research narrated here would not have been possible without the creativity and dedication of my outstanding lab members or without the contributions from my outstanding external collaborators.

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Authors and Affiliations

  1. Department of Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada

    A. Claudio Cuello

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  1. A. Claudio Cuello
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Correspondence to A. Claudio Cuello .

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Editors and Affiliations

  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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I would like to dedicate these reflections about trophic responses not only to the memory of Rita Levi Montalcini and her stellar career, but also as a tribute to Mario Bunge’s legacy. He was one of the world’s greatest philosophers of his generation. A philosopher with formal and deep knowledge of the physical and biological sciences. A philosopher who understood synaptic plasticity and who strongly made the case that mind, consciousness, and all psychological responses were strictly governed by neuronal connections and biochemical brain events. I had the privilege of sharing with Mario many interminable scientific discussions and with him and his family many memorable events. I will sorely miss his loss as a dear friend and as an inspiring McGill colleague.

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Cuello, A.C. (2021). Rita Levi-Montalcini, NGF Metabolism in Health and in the Alzheimer’s Pathology. 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_9

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