Cathepsin D deficiency and NCL/Batten disease: there's more to death than apoptosis.
Animal models of cathepsin D (CD) deficiency are characterized by a progressive and relentless neurodegenerative phenotype similar to that observed in Neuronal Ceroid Lipofuscinoses (NCL), a group of pediatric neurodegenerative diseases known collectively as Batten Disease. We have shown recently that the targeted deletion of the pro-apoptotic molecule Bax prevents apoptotic markers but not neuron death and neurodegeneration induced by CD deficiency, which suggests that alterations in the macroautophagy-lysosomal degradation pathway can mediate neuron death in NCL/Batten Disease in the absence of apoptosis. Herein, we review CD deficiency in the broader context of NCL and offer potential mechanisms for neuron death and neurodegeneration induced by CD deficiency.
Shacka
John J
JJ
Department of Pathology, Neuropathology Division, University of Alabama at Birmingham, Birmingham, Alabama 35294-0017, USA. shacka@uab.edu
Roth
Kevin A
KA
D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D002402:Cathepsin D / Q000172:deficiency* / Q000235:genetics; D006801:Humans; D009154:Mutation; D009410:Nerve Degeneration / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D009472:Neuronal Ceroid-Lipofuscinoses / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D009474:Neurons / Q000473:pathology
D002402:Cathepsin D