Humanin Expression and Subcellular Localisation in Cardiac Amyloidosis: Insights into Its Post-Translational Regulation

Cardiac amyloidosis is a progressive cardiomyopathy caused by the deposition of misfolded proteins in the myocardium, leading to structural remodelling, cellular dysfunction and heart failure. Despite advances in diagnosis and treatment, the molecular mechanisms underlying myocardial injury and adaptation to amyloid-associated stress remain incompletely understood, and mitochondrial dysfunction is an emerging contributor to disease progression. Humanin is a mitochondrial-derived peptide involved in cytoprotection, apoptosis, metabolism and oxidative stress responses, and may protect cells from stress-related injury. However, its expression and localisation in cardiac amyloidosis have not been systematically characterised, and the mechanisms regulating its biological availability are unknown. This project aims to characterise Humanin expression and localisation in cardiac amyloidosis and to investigate mechanisms potentially involved in its post-translational regulation. Cardiac tissue samples will be analysed using histological, immunohistochemical, immunofluorescence and molecular approaches to define Humanin distribution and its relationship with amyloid deposits and myocardial cellular compartments. Mechanisms affecting Humanin processing, stability, degradation and intracellular localisation will also be explored. The project will provide new insights into the role of mitochondrial-derived peptides in the myocardial response to amyloid-associated stress. Changes in Humanin expression or localisation, and the mechanisms regulating its availability, may reveal novel pathways of myocardial injury and adaptation, supporting the evaluation of Humanin as a candidate biomarker and providing a basis for future studies on its therapeutic potential.