Physiological functions and pathobiology of TDP-43 and FUS/TLS proteins

摘要: The multiple roles played by RNA binding proteins in neurodegeneration have become apparent following the discovery of TAR DNA protein 43 kDa (TDP-43) and fused sarcoma/translocated liposarcoma (FUS/TLS) involvement amyotrophic lateral sclerosis frontotemporal lobar dementia. In these two diseases, majority patients display presence aggregated forms one their brains. study functional properties currently represents a very promising target for developing effective therapeutic options that are still lacking. This aim, however, must be preceded an accurate evaluation TDP-43 FUS/TLS biological functions, both physiological disease conditions. Recent findings uncovered several aspects metabolism can affected misregulation proteins. Progress has also been made starting to understand how aggregation occurs spreads from cell cell. aim this review will provide general overview highlight functions. At present, emerging picture is control mRNA's life, but they participate repair processes non-coding metabolism. Although regulatory activities similar, regulate mainly distinct targets show different pathogenetic mechanisms sclerosis/frontotemporal dementia diseases. identification key events today best chance finding targetable approaches might actually make difference at clinical level. major Binding Proteins involved Amyotrophic Lateral Sclerosisi Frontotemporal Dementia FUST/TLS. Both regulating all life cycle within neurons, transcription, processing, transport/stability formation cytoplasmic nuclear stress granules. For reason, aberrant factors during impair metabolic pathways eventually lead neuronal death/inactivation. purpose up-to-date perspective on what we know about issue molecular article part the Frontotemporal special issue.