Topic: 4-aminopyridine

Haploinsufficiency of the CACNA1A gene, encoding the pore-forming α1 subunit of P/Q-type voltage-gated calcium channels, is associated with a clinically variable phenotype ranging from cerebellar ataxia, to neurodevelopmental syndromes with epilepsy and intellectual disability. To understand the pathological mechanisms of CACNA1A loss-of-function variants, we characterized a human neuronal model for CACNA1A haploinsufficiency, by differentiating isogenic induced pluripotent stem cell lines into glutamatergic neurons, and investigated the effect of CACNA1A haploinsufficiency on mature neuronal

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