Batten's disease: Clues to neuronal protein catabolism in lysosomes

Neuronal ceroid lipofuscinosis (Batten disease) encompasses a group of 8 or more inherited lysosomal storage diseases, with an overall frequency of 1 in 12,500 births. All are characterized by progressive blindness and dement ia and were initially classified on the basis of age of onset, clinical phe notype and ultrastructural characterization of the storage material as gran ular osmiophilic deposits, curvilinear bodies or fingerprint bodies. Recent research has shown that the various forms of Batten disease result from mu tations in at least 8 genes which code for proteins involved in different a spects of lysosomal protein catabolism. These include palmitoyl:protein thi oesterase I(CLN1), tripeptidylpeptidase I(CLN2), cathepsin D (CLN8), and tw o membrane proteins of unknown function (CLN3 and CLN5). Biochemically, Bat ten disease is characterized by the accumulation in neurons and other cells of an autofluorescent pigment which has resisted many attempts at analysis . In this review we attempt to relate our current understanding of the natu re of the storage material in Batten disease with this genetic information. We conclude that the 8 genes probably code for proteins which facilitate t he degradation of post-translationally modified proteins in lysosomes, sugg esting that the turnover of these proteins is highest in cortical neurons.( C) 2000 Wiley-Liss, Inc.