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We characterize the metabolic background in distinct Acute Myeloid Leukemias (AMLs), by comparing the metabolism of primary AML blasts isolated at diagnosis with that of normal hematopoietic maturing progenitors, using the Seahorse XF Agilent. Leukemic cells feature lower spare respiratory (SRC) and glycolytic capacities as compared to hematopoietic precursors (i.e. day 7, promyelocytes). According with Proton Leak (PL) values, AML blasts can be grouped in two well defined populations. The AML group with blasts presenting high PL or high basal OXPHOS plus high SRC levels had shorter overall survival time and significantly overexpressed myeloid cell leukemia 1 (MCL1) protein. We demonstrate that MCL1 directly binds to Hexokinase 2 (HK2) on the outer mitochondrial membrane (OMM). Overall, these results suggest that high PL and high SRC plus high basal OXPHOS levels at disease onset, arguably with the concourse of MCL1/HK2 action, are significantly linked with shorter overall survival time in AML. Our data describe a new function for MCL1 protein in AMLs’ cells: by forming a complex with HK2, MCL1 co-localizes to VDAC on the OMM, thus inducing glycolysis and OXPHOS, ultimately conferring metabolic plasticity and promoting resistance to therapy.

The association between diabetes and neurodegenerative diseases is increasing with aging. Several common mechanisms are involved in both these diseases. The endothelial cells of the blood brain barrier, neurons and glia express typical and different receptors of the glucose metabolism (glucose transporters, insulin receptors and glucagon-like peptide-1 receptors). The impairment in insulin signaling leads to an impairment of neuronal function and increases neurodegeneration, and, conversely, neurodegeneration causes a reduction of insulin signaling on neurons. Increased detailed knowledge of common physiological processes opens up the opportunities for developing new treatments that may prevent or reduce the onset of neurodegenerative diseases. The aim of the review is to discuss the potential neuroprotective effects of the antidiabetic drugs. The article presents somepromising patents on the treatment of insulin resistance in the neurodegeneration.

Among several types of DNA lesions, the DNA double strand breaks (DSBs) are one of the most deleterious and harmful. Mammalian cells mount a coordinated response to DSBs with the aim of appropriately repair the DNA damage. Indeed, failure of the DNA damage response (DDR) can lead to the development of cancer-prone genetic diseases. The identification and development of drugs targeting proteins involved in the DDR is even more investigated, as it gives the possibility to specifically target cancer cells. Indeed, the administration of DNA repair inhibitors could be combined with chemo- and radiotherapy, thus improving the eradication of tumor cells. Here, we provide an overview about DSBs damage response, focusing on the role of the DSBs repair mechanisms, of chromatin modifications, and of the cancer susceptibility gene BRCA1 which plays a multifunctional role in controlling genome integrity. Moreover, the most investigated DSBs enzyme inhibitors tested as potential therapeutic agents for anti-cancer therapy are reported.

In our review entitled ‘Therapeutic Drug Monitoring in the Management of HIV-Infected Patients’ in the Current Medicinal Chemistry, 2008, 15(19), 1925-39.