Abstract
Neuronal ceroid lipofuscinosis (NCL) is an umbrella term referring to the most frequent childhood-onset neurodegenerative diseases, which are also the main cause of childhood dementia. Although the molecular mechanisms underlying the NCLs remain elusive, evidence is increasingly pointing to shared disease pathways and common clinical features across the disease forms. The characterization of pathological mechanisms, disease modifiers, and biomarkers might facilitate the development of treatment strategies.
The DEM-AGING project aims to define molecular signatures in NCL and expedite biomarker discovery with a view to identifying novel targets for monitoring disease status and progression and accelerating clinical trial readiness in this field. In this study, we fused multiomic assessments in established NCL models with similar data on the more common late-onset neurodegenerative conditions in order to test the hypothesis of shared molecular fingerprints critical to the underlying pathological mechanisms. Our aim, ultimately, is to combine data analysis, cell models, and omic strategies in an effort to trace new routes to therapies that might readily be applied in the most common forms of dementia.
Data Availability
Data will be made available on request at sdoccini@fsm.unipi.it.
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Acknowledgements
We thank C.J. Wrenn for editorial assistance. M.M. is the holder of the Telethon Career Award. N.G. holds a PhD fellowship in neuroscience, University of Florence, Italy. AS is a member of the European Reference Network MetabERN. Members of the DEM-AGING network are listed in Supplementary table S3.
Funding
This research project is funded by: Regione Toscana (Bando Ricerca Salute 2018, project DEM AGING), by the Italian Ministry of Health, Ricerca Corrente2023 e RC 5 × 1000 (to S.D. and F.M.S.), and Ricerca Finalizzata 2018, Starting Grant (SG-2018–12367839) (to M.M.), and by a Telethon Foundation (grant GGP20011) to M.M.
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Gammaldi, N., Doccini, S., Bernardi, S. et al. Dem-Aging: autophagy-related pathologies and the “two faces of dementia”. Neurogenetics 25, 39–46 (2024). https://doi.org/10.1007/s10048-023-00739-3
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DOI: https://doi.org/10.1007/s10048-023-00739-3