CARDIAC DYSFUNCTION AS EVIDENCE OF PERIPHERAL ORGAN INVOLVEMENT IN NEURODEGENERATION

Neurodegenerative diseases (ND) comprise a varied array of disorders characterized by the gradual decline of neuronal structure and function. These conditions significantly contribute to global morbidity and mortality. Despite progress in symptomatic management, existing therapies do not target the underlying causes, underscoring the necessity for more profound mechanistic understanding. Although the majority of research has concentrated on the central nervous system (CNS), emerging evidence indicates that peripheral organs, such as the heart, liver, muscles, and kidneys, are likewise impacted. Nonetheless, their participation remains inadequately examined. Prior research has indicated a decline in neuronal innervation, the presence of pathological protein aggregates, and alterations in electrocardiographic (ECG) parameters in neurodegeneration (ND). The precise effect on cardiac function remains inadequately comprehended. This study investigated cardiac pathology in cellular and murine models of neurodegenerative disorder. Our findings demonstrated significant cardiac anomalies. These encompassed hypertrophy and fibrosis, as well as disruptions in cellular quality-control mechanisms, including the ubiquitin-proteasome and autophagic pathways. We observed the aggregation of ubiquitin and p62, reflecting patterns observed in the neurodegenerative brain. RNA-seq revealed distinct gene expression patterns, highlighting differences in molecular pathways. The ECG analysis revealed anomalous PQRST waveforms, modified heart rate, and diminished heart rate variability, signifying compromised cardiac function. We also identified potential mechanisms underlying these alterations, including mitochondrial dysfunction and reduced neuronal innervation. Collectively, our findings illuminate the cardiac manifestations of neurodegeneration and emphasise the necessity of examining peripheral organ involvement to enhance therapeutic strategies and expand our comprehension of neurodegeneration.