👤 Kynen Piacentini

Parkinson's disease (PD) is a complex neurodegenerative disease that involves many interlinking pathways and genetic elements that remain to be fully understood and characterised. Non-coding genetic elements have long been overlooked, however recent advancements in the field have highlighted their importance with an area of interest being transposable elements. SINE-VNTR-Alu (SVA) elements are the youngest and smallest subset of retrotransposons that are only found within hominid species. SVAs have been shown to have strong regulatory impacts within our genome and can affect progression of neurodegenerative disease such as PD. Previous studies identified an SVA, polymorphic for its presence/absence, that was associated with changes in gene expression at the Show less

Over the last two decades, the use of Next-Generation Sequencing (NGS) in medical oncology has increased the likelihood of identifying druggable mutations that may be potentially susceptible to targeted treatments. The European Society for Medical Oncology (ESMO) currently does not recommend the use of the NGS test to determine the therapeutic course of patients with metastatic breast cancer (mBC) in daily clinical practice. However, the aim of this work is to evaluate the potential contribution of the NGS test in selecting targeted therapies for patients with mBC. Data were retrospectively collected from 101 patients diagnosed with metastatic breast cancer and treated at the Modena Cancer Center between January 2015 and April 2022. A NGS test was performed on the tumor tissue of each patient at the Laboratory of Molecular Pathology of the University Hospital of Modena. This study analyzed the clinical-pathological characteristics and mutational profile of the population using NGS tests, with a focus on actionable mutations that could be targeted in advanced stages of clinical development. The indicator of this study was to quantify the actionable mutations that resulted in a change of cancer treatment. In total, 101 patients with metastatic breast cancer were analyzed, including 86 with luminal phenotype, 10 who were HER2-positive and 5 who were triple-negative. Median age was 52 years. NGS analysis was conducted on 47 samples of primary breast cancer, 52 on metastatic sites of disease and 2 on liquid biopsies. A total of 85 gene mutations were found. The most common mutations were identified in the Show less

Aging is a gradual and irreversible physiological process that significantly increases the risks of developing a variety of pathologies, including neurodegenerative, cardiovascular, metabolic, musculoskeletal, and immune system diseases. Mitochondria are the energy-producing organelles, and their proper functioning is crucial for overall cellular health. Over time, mitochondrial function declines causing an increased release of harmful reactive oxygen species (ROS) and DNA, which leads to oxidative stress, inflammation and cellular damage, common features associated with various age-related pathologies. The impairment of mitophagy, the selective removal of damaged or dysfunctional mitochondria by autophagy, is relevant to the development and progression of age-related diseases. The molecular mechanisms that regulates mitophagy levels in aging remain largely uncharacterized. AMBRA1 is an intrinsically disordered scaffold protein with a unique property of regulating the activity of both proliferation and autophagy core machineries. While the role of AMBRA1 during embryonic development and neoplastic transformation has been extensively investigated, its functions in post-mitotic cells of adult tissues have been limited due to the embryonic lethality caused by AMBRA1 deficiency. Recently, a key role of AMBRA1 in selectively regulating mitophagy in post-mitotic cells has emerged. Here we summarize and discuss these results with the aim of providing a comprehensive view of the mitochondrial roles of AMBRA1, and how defective activity of AMBRA1 has been functionally linked to mitophagy alterations observed in age-related degenerative disorders, including muscular dystrophy/sarcopenia, Parkinson diseases, Alzheimer diseases and age-related macular degeneration. Show less

BCKDK is an important key regulator of branched-chain ketoacid dehydrogenase complex activity by phosphorylating and so inactivating branched-chain ketoacid dehydrogenases, the rate-limiting enzyme of the branched-chain amino acid metabolism. We identified, by whole exome-sequencing analysis, the p.His162Gln variant of the Show less