From the Scientific Underground to the Height of Recognition: The 40th Anniversary of Rita Levi-Montalcini's Nobel Prize and the Promising Horizon in Psychiatry.

Forty years ago, in 1986, Rita Levi-Montalcini was awarded the Nobel Prize in Physiology or Medicine for the discovery of Nerve Growth Factor, a fundamental finding that inaugurated the field of trophic signaling in the nervous system. Her research, conducted with credibility and consistency under the precarious conditions of an Italy enduring the Second World War, and later refined in the United States, rigorously demonstrated that neuronal growth and survival are regulated by specific chemical signals, not merely by intrinsic processes. Using biological assays involving sarcoma and chicken embryos, Levi-Montalcini identified a protein substance that promoted exuberant nerve fiber growth from sensory and sympathetic ganglia. The subsequent purification and biochemical characterization of Nerve Growth Factor by biochemist Stanley Cohen - with whom she shared the Nobel Prize - confirmed its protein nature. This discovery scientifically proved the existence of signaling molecules that guide nervous system development, including critical processes such as neuronal differentiation, axonal growth, and apoptosis, programmed cell death. The concept that target-cells secrete trophic factors for maintenance and survival became fundamental in neuroembryology. The impact of Levi-Montalcini's work transcended developmental neurobiology. The Nerve Growth Factor model paved the way for the discovery of a family of neurotrophins, elucidating mechanisms of neural plasticity, regeneration, and brain aging, with profound implications for the understanding of mental illnesses, neurodegenerative diseases, and cancer. For establishing, with experimental precision, a universal principle of cellular communication in the nervous system, Rita Levi-Montalcini - a scientist who expanded scientific frontiers - was honored with numerous awards, alongside the Nobel Prize, consolidating her position as an influential female figure in 20th-century neuroscience.