Axonal injury under the – super-resolution – microscope

At the LCSB, the Chemical and Molecular Neurobiology group led by Prof. Ivana Nikić-Spiegel bridges microscopy and chemical biology to decipher the molecular mechanisms behind brain diseases, in particular multiple sclerosis, and identify ways to protect neurons from injury. Their approach: Using nanoscale imaging and advanced molecular tools to get a better overall picture of neurodegeneration.

Spotlight on multiple sclerosis

The group focuses on multiple sclerosis, a chronic neurological disorder that affects 2,8 millions people worldwide – mostly young adults – and presents with very heterogeneous symptoms. Current treatments can delay the long-term progression of the disease but there is no cure for multiple sclerosis, placing a heavy burden on patients and societies. “Multiple sclerosis is characterised by the formation of lesions in the brain and spinal cord. These arise from inflammation, driven by immune cells, that damages myelin, the protective coating of nerve fibres, and can also injure the nerve fibres themselves,” explains Prof. Nikić-Spiegel. “As a result, communication within the nervous system is disrupted, contributing to disability over time. However, the molecular mechanisms underlying these processes are still not fully understood.”

This is where the group’s unique technical expertise comes in. Combing imaging, from live-cell to super-resolution microscopy, chemical biology and proteomics, the researchers explore the organisation and dynamics of proteins within brain cells. By labelling newly synthetised proteins in a given cell type and during a specific time frame, they are able to investigate processes that get disrupted by the disease. “We first conduct untargeted proteomics studies to find out which proteins are up- or downregulated in different phases of multiple sclerosis. It helps us pinpoint proteins of interest that could constitute good target for treatments,” details Prof. Nikić-Spiegel.

Live imaging and super-resolution microscopy to observe proteins

A brand-new microscope recently installed at the LCSB allows the team to visualise proteins or protein clusters measuring just 10 to 15 nanometres, opening new possibilities to understand how alterations in molecular organisation contribute to neuronal dysfunction.

Finding commonalities across neurodegenerative diseases

By harnessing the power of cutting-edge technologies and developing new methodologies for their use in complex systems such as cell cultures and in vivo models, the Chemical and Molecular Neurobiology group aims not only to unravel the molecular mechanisms of multiple sclerosis, but also to find commonalities with other brain diseases.

“Processes such as oxidative stress and neuroinflammation play a role in all these disorders. Similarly, beyond its well-established role in multiple sclerosis, myelin is emerging as an important factor in other neurodegenerative diseases,” underlines Prof. Nikić-Spiegel. “So, we hope that our findings on how to protect the nervous system from axonal injury and demyelination could translate from multiple sclerosis to Parkinson’s and Alzheimer’s disease.”