Luciano D'Adamio, M.D., Ph.D., is currently a Professor of Immunology at Albert Einstein College of Medicine in New York. After graduating from medical school in Perugia (Italy), he started his PhD program at the University "La Sapienza" (Rome, Italy). Most of his PhD work was done as a collaboration project at the Dana-Farber Cancer Institute, Harvard Medical School (Boston, USA). At Dana-Faber Luciano, under the supervision of Dr. Ellis L. Reinherz, demonstrated that autoreactive T cells during thymic development are eliminated by an apoptotic mechanism. Soon after Luciano became a principal investigator in the Laboratory of Cellular and Molecular Immunology, National Institute of Allergy & Infectious Diseases, NIH (Bethesda, USA). At the NIH he developed a functional selection system to identify genes regulating apoptosis in T cells. One of the genes isolated by him and his collaborators encodes for a fragment of the Familial Alzheimer's Disease (FAD) gene Presenilin-2 (PS2). Luciano showed that this PS-2 fragment could inhibit apoptotic responses to stimulation of membrane death receptors such as Fas and TNFRI. Subsequently, Luciano's team proved that PS2 is required for apoptosis and that PS2 FAD mutants have enhanced pro-apoptotic activity. Some FAD cases are linked to mutations in genes encoding presenilin1 (PS1) and presenilin-2 (PS2), both proteins required for gamma-secretase activity and therefore involved in the processing of AβPP, the third FAD gene known to date. Luciano is continuing his study on the biology of Presenilins and AβPP as an Irene Diamond Associate Professor of Immunology in the Department of Microbiology and Immunology, Albert Einstein College of Medicine (NY, USA) with his own research group.

Importance of published article

Luciano's main contribution in the apoptosis field lays in the observation that genes implicated in AD can regulate programmed cell death (PCD). These observations suggested a possible key role of apoptosis in the generation of AD. In his JAD paper "Generation of an Apoptotic Intracellular Peptide by gamma-secretase Cleavage of Alzheimer's Amyloid β Protein Precursor" he clearly demonstrates that an "Apoptotic Theory" can be considered to greatly contribute to the disease and can further explain the classical "Amyloid Theory". In fact, while the general believe of the cause of AD is a deposition of the amyloidogenic form of Aβ peptide, Luciano showed that the γ-secretase cleavage of AβPP releases, together with the Aβ peptide, also a C-terminal intracellular domain that he called AID. AID is able to induce apoptosis in different cell lines. Identifying AID-like peptide in brain tissues of AD patients and demonstrating that AID acts as a positive regulator of apoptosis, he was able to provide for the first time an alternative explanation for the pathogenesis of AD. Increased steady-state levels of AID in AD cases may initially cause biochemical alteration and neuronal disfunction. Prolonged alterations in neuronal metabolism may progressively lead to neuronal degeneration and death. The general unifying concept between the two theories is that AßPP processing by gamma-secretase generates peptides that regulate PCD.

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