Topic: CLN1

The complexity of neurodegenerative processes and the human nervous system hinder progress towards a comprehensive understanding of both. Much of our advancements in understanding disease has been through the use of human post-mortem tissues. As these are only representative of the end stage of life, it is difficult to differentiate between chronic long-term consequences of disease (ie, neurofibrillary tangles) and potential regulators which directly drive pathological processes. Using small animal model systems has limitations resulting in high failure to translate directly from rodent-derive

Infantile neuronal ceroid lipofuscinosis (INCL) is a rare lysosomal storage disorder caused by mutations in the Cln1 gene, which encodes the Palmitoyl-Protein Thioesterase 1 (PPT1) enzyme. Like human patients, mutant mice exhibit defective autophagy, leading to widespread neuronal death accompanied by symptoms such as epilepsy, retinal and cortical degeneration, and premature death (Gupta, 2001). However, the precise mechanism linking Cln1 mutation to hyperexcitability and altered brain processing remains poorly understood. First, video-recordings in an open field arena demonstrated that CLN1