Advances in the study of organelle interactions and their role in neurodegenerative diseases enabled by super-resolution microscopy

From the first illustrations of neuronal morphology by Ramón y Cajal to the recent three-dimensional reconstruction of synaptic connections, the development of modern neuroscience has greatly benefited from breakthroughs in imaging technology. This also applies specifically to the study of neurodegenerative diseases. Much of the research into these diseases relies on the direct visualisation of intracellular structures and their dynamics in degenerating neural cells, which cannot be fully resolved by diffraction-limited microscopes. Progress in the field has therefore been closely linked to the development of super-resolution imaging methods. Their application has greatly advanced our understanding of disease mechanisms, ranging from the structural progression of protein aggregates to defects in organelle morphology. Recent super-resolution studies have specifically implicated the disruption of inter-organelle interactions in multiple neurodegenerative diseases. In this article, we describe some of the key super-resolution techniques that have contributed to this field. We then discuss work to visualise changes in the structure and dynamics of organelles and associated dysfunctions. Finally, we consider what future developments in imaging technology may further our knowledge of these processes