14 different genes have been linked to NCLs (CLN1-CLN14), but the functions of the proteins encoded by the majority of these genes have not been fully elucidated.
Caenorhabditis elegans dnj-14, the orthologue of the DNAJC5 gene mutated in adult onset neuronal ceroid lipofuscinosis, provides a new platform for neuroprotective drug screening and identifies a SIR-2.1-independent action of resveratrol.
In humans, CSPα mutations are associated with the development of neuronal ceroid lipofuscinosis (NCL), a neurodegenerative disease characterized by intracellular accumulation of lysosomal material.
It also confirms a neuroprotective role for CSPα in humans and demonstrates the need for detailed investigation of CSPα in the neuronal ceroid lipofuscinoses and other neurodegenerative diseases presenting with neuronal protein aggregation.
Mutations or overexpression of the wild type form of α-synuclein have been related to Parkinson's disease, and CSPα mutations cause one type of neuronal ceroid lipofuscinosis.
We propose that this palmitoylation-induced aggregation of mutant CSPα proteins may underlie the development of adult-onset neuronal ceroid lipofuscinosis in affected families.