Chun-Hung Chan and David A. Pearce Pages 257 - 268 ( 12 )
The neuronal ceroid lipofuscinoses (NCL) are the most common childhood neurodegenerative disorders with a worldwide incidence of up to 1 in 12, 500 live births. Various subtypes have been described on a clinical and genetic level, with mutations in one of at least eight genes, termed CLN1-8, forming the molecular basis of the disease. Since mutations in distinct genes result in similar pathologies, suggesting a common biological pathway, it is important to not only elucidate the function of the proteins they encode but also to examine the possible consequences of protein dysfunction in cellular processes. Development of animal models of NCL disease and advancements in genomic and proteomic technologies provide valuable tools in the search for the underlying basis of disease. Application of DNA microarray analysis has revealed alterations in the expression of genes involved in a number of cellular processes including inflammation, neuronal function, oxidative stress, energy metabolism and proteolytic processing. Comparison of DNA microarray data from various NCL animal models has revealed not only alterations in a number of common pathological pathways characteristic of neurodegenerative disorders, but also some unique changes that may provide an insight into the function of the mutated proteins that underlie these diseases. Here, we review and discuss how such studies have furthered our current understanding of protein function and related pathological processes.
Neuronal Ceroid, proteolytic, neuronal ceroid lipofuscinoses (NCL), neurodegenerative
Center for Aging and Developmental Biology, Department of Biochemistry and Biophysics, Box 645,University of Rochester, School of Medicine and Dentistry, Rochester, New York 14642, USA.