Publications by authors named "A Catanese"
The pathogenic expansion of the intronic GGGGCC hexanucleotide located in the non-coding region of the gene represents the most frequent genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). This mutation leads to the accumulation of toxic RNA foci and dipeptide repeats (DPRs), as well as reduced levels of the C9orf72 protein. Thus, both gain and loss of function are coexisting pathogenic aspects linked to -ALS/FTD.
View Article and Find Full Text PDFSpinal motor neurons (MNs) represent a highly vulnerable cellular population, which is affected in fatal neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA). In this study, we show that the heterozygous loss of SYT13 is sufficient to trigger a neurodegenerative phenotype resembling those observed in ALS and SMA. SYT13 hiPSC-derived MNs displayed a progressive manifestation of typical neurodegenerative hallmarks such as loss of synaptic contacts and accumulation of aberrant aggregates.
View Article and Find Full Text PDFArticle Synopsis
- Heterozygous mutations in the TBK1 gene are linked to neurodegenerative diseases like ALS and FTD, with most patients carrying harmful loss-of-expression mutations.
- The study focused on the p.E696K missense variant of TBK1, which doesn't completely stop protein expression but disrupts its interaction with the autophagy protein optineurin.
- Research showed that this mutation leads to early dysfunction in neuron recycling processes, resulting in damaged lysosomes and eventually causing a progressive motor neuron disease, highlighting potential therapeutic targets for treatment.