A study published in Brain by researchers from the University of Trento and international collaborators provides new insights into amyotrophic lateral sclerosis (ALS), focusing on the role of glial cells in the disease's progression.
Key Findings
- The study examined a slow-progression model of ALS and found that astrocytes and oligodendrocytes play a role in pathogenesis.
- Altered function of the TDP-43 protein, observed in 97% of ALS patients, was corrected, revealing that glial cells behave differently over time: early in the disease they de-differentiate (lose specialized functions that support neurons), while late stages show increased inflammation in all glial cells.
- The factor MYC was identified as responsible for glial cell abnormality: hyperactive MYC pushes glial cells to become inflammatory and release small vesicles that make neurons more vulnerable.
- These signals were observed in patients' cerebrospinal fluid, suggesting vesicles could serve as biomarkers for diagnosis and monitoring.
Implications
MYC factor may be a new molecular target to induce glial cells to support neurons again.
- Further research is needed to understand if glial de-differentiation and inflammation occur in all patients, and to verify biomarkers that could group patients into subgroups for more effective therapy.
- The research group will also investigate the timing of glial activation windows (de-differentiation, proliferation, neuroinflammation) to optimize therapeutic approaches.
Study Details
The study involved 51 researchers from Italy, Spain, the United Kingdom, the United States, Lebanon, and Japan. Funding was provided by Fondazione AriSla, the Ministry of University and Research, the Ministry of Health, and donations to the University of Trento.