Learning outcomes

The aim of this course is to cover a few general mechanisms of cell damage, giving information useful to understand the development of molecular pathology towards cell, tissue and organism pathology. The course covers the most important examples of damage to sub-cellular structures, particularly to the plasma membrane, describing in some details examples of alterations of transport, adhesion and signal transduction by membrane receptors. Different type of cell necrosis, factors determining regeneration or repair of injured tissues and molecular and cellular basis of reparative reactions and their pathologic consequences are also illustrated.

Program

- Introduction to mechanisms of disease: from molecular pathology to alteration of tissue and organism homeostasis.
- Adaptation to cell injury: autophagy, unfolded protein response, alterations in cell volume and number.
- Forms of cell necrosis: necrosis, apoptosis, necroptosis and nettosis.
- General aspect of tissue regeneration and repair: from the concept of labile, stable and permanent cells to recent aspects of stem cell biology.
- Causes of cell pathology: major causes and highlighting of reactive oxygen specie generation as a key cause of cell pathology. Alterations of specific genes as a cause of tumor emergence and the principal hallmarks of cancer cells.
- Alterations of mitochondrial functions as a mechanism of cell pathology: mitochondrial diseases, role of mitochondria in cell aging, mitochondria and induction of apoptosis.
- Alterations of cell membrane structure induced by bacterial toxins and general mechanism of bacterial toxin action.
- Alterations of membrane transport: examples of alterations of anion and cation transport; cystic fibrosis as an example of a monogenic disease causing multiple organ pathology; alterations of lipid transport due to ABC protein mutation (Tangier disease, sitosterolemia) and geneal aspects of lipoprotein metabolism; alterations of iron transport in chronic inflammation and emocromatosis.
- Alterations of LDL-receptor expression and function as an example of molecular pathology leading to organisms pathology: classification of lipoprotein receptors; familiar hypercholesterolemia as a genetic form of deficient expression/function of the LDL-receptor; mechanisms of regulation of LDL-receptor expression by cell cholesterol; from reduced LDL-receptor expression to atherosclerosis (role of modified LDL as a cause of development of the atherosclerotic plaque and cellular basis of atherosclerosis).
- Alterations of expression/function of adhesive receptors: general aspects of cell adhesion; integrins as the most widely expressed adhesion molecules implicated in cell-extracellular matrix interaction (classification and ligands); mechanisms of regulation of integrin adhesion (inside-out signaling).
- Adhesive interactions implicated in leukocyte recruitment into inflammatory sites: physiology and pathology.
- Adhesive interactions implicated in the function of platelets in hemostatic reaction and mechanisms of activation of platelets.
- The coagulation system, the soluble component of hemostatic reactions: mechanisms of activation and negative regulation.
- Deficit of hemostatic functions and the etiopathogenesis of thrombosis.
- Physiopathology of signal transduction: general aspects and modality of signal transduction by membrane surface receptors.
- Signal transduction by receptors with an intrinsic tyrosine kinase activity: the Ras and the PI3K pathways; downstream targets of PIP3; AKT in regulation of cell growth, survival and metabolism; receptor tyrosine kinase mutations in cancer; development of tyrosine kinase inhibitors.
- The insulin receptor: mechanisms of signal transduction; the concept of insulin resistance and alterations of insulin signal transduction in type 2 diabetes; obesity, inflammation and type 2 diabetes.
- Mechanisms of signal transduction by trimeric G protein-coupled receptors: regulation of trimeric G proteins; down-stream effectors of Galpha-GTP and beta/gamma subunit of trimeric G proteins.
- Activation of phosphoinositide-specific Phospholipases C and regulation of cytoplasmic calcium transients.
- Trimeric G protein-coupled receptors, PI3Kgamma and regulation of cell migration.
- Cytoplasmic tyrosine kinases as signal transducers: major classes of cytoplasmic tyrosine kinases; mechanisms of regulation of Src and Abl kinases; cytoplasmic tyrosine kinases in integrin outside-in signaling and regulation of cytoskeleton rearrangements and cell survival; cytoplasmic tyrosine kinases and signal transduction by immune receptors.
- Other mechanisms of signal transduction by surface receptors: signal transduction by cadherins; signal transduction by Toll-like receptors and pathogenesis of the septic shock.
- Pathology of contractile cells: muscular dystrophies; mechanisms of cardiac hypertrophy.

Bibliografia

Examination Methods