Progress towards understanding the neurobiology of Batten disease or neuronal ceroid lipofuscinosis

Purpose of review: The identification of genes mutated in the neuronal ceroid lipofuscinoses has accelerated research into the mechanisms that underlie these fatal autosomal recessive storage disorders, which are often referred to as Batten disease. This review summarizes progress in this field since October 2001, describing advances in cell biology, the characterization of new animal models of neuronal ceroid lipofuscinosis, and the impact of novel methodology to reveal insights into its pathogenesis. Recent findings: Gene products for six of the eight forms of neuronal ceroid lipofuscinosis have now been discovered, and concerted efforts are underway to understand the normal biology of each gene product and how this may be altered by mutation. Several lines of evidence point to functions for the CLN genes in the endosomal-lysosomal system, and suggest neuron-specific roles for these proteins. Indeed, a requirement for appropriate protein trafficking within neurons may explain the profound and selective effects of these disorders upon the central nervous system. The development of mouse and large animal models has enabled comparative studies of the progressive effects of disease, including characterization by morphological and biochemical means supplemented by metabonomic and microarray techniques. Summary: Insights into disease mechanisms are building a detailed profile of the impact of neuronal ceroid lipofuscinosis upon the brain. With the eventual aim of developing successful therapeutic strategies, it will be equally important to characterize the clinical progression of the disorder, and to identify quantifiable endpoints that can ultimately be used in clinical trials.