A genome-wide approach unravels neurodegeneration
NCLs are a group of inherited childhood encephalopathies that are characterised by the progressive death of central nervous system (CNS) neurons. Although their phenotype has long been reported, our knowledge on the mechanisms responsible for the observed neurodegeneration is limited. The EU-funded ‘Dissecting neuronal degeneration: Neuronal ceroid lipofuscinoses from genes to function’ (NCL-Models) project aimed to address this issue and investigate the role of NCL proteins in NCLs. NCL disorders also provide an excellent model for studying molecular events that lead to neurodegeneration in general. Various molecular and genetic techniques were used to study the pathogenic mechanisms of the NCLs in models such as mammalian cells, yeast and mouse. Genome-wide analysis combined with proteomics data were used to study these disease models in detail. Scientists looked at how NCL proteins were implicated in neuronal metabolism and neuronal death. The NCL-Models collaborative efforts resulted in several major achievements towards our understanding of NCL neurobiology. Insights into the cellular processes that influence neuronal death and ageing have the potential to be extended to other neurological disorders as well. The knowledge acquired is expected to benefit NCL patients and the quality of life of families affected by this major paediatric neurodegenerative disease.
