title: TDP-43 functions and pathogenic mechanisms implicated in TDP-43 proteinopathies.
abstract: Given the critical role for TDP-43 in diverse neurodegenerative diseases including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD-TDP), there has been a recent surge in efforts to understand the normal functions of TDP-43 and the molecular basis of dysregulation that occurs in TDP-43 proteinopathies. Here, we highlight recent findings examining TDP-43 molecular functions with particular emphasis on stress-mediated regulation of TDP-43 localization, putative downstream TDP-43 target genes and RNAs, as well as TDP-43 interacting proteins, all of which represent viable points of therapeutic intervention for ALS, FTLD-TDP and related proteinopathies. Finally, we review current mouse models of TDP-43 and discuss their similarities and potential relevance to human TDP-43 proteinopathies including ALS and FTLD-TDP.
authors.affiliation: Department of Pathology and Laboratory Medicine, Institute on Aging and Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Todd J
authors.initials: TJ
authors.lastname: Cohen
authors.forename: Virginia M Y
authors.initials: VM
authors.lastname: Lee
authors.forename: John Q
authors.initials: JQ
authors.lastname: Trojanowski
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism; D020125:Mutation, Missense; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping; D012333:RNA, Messenger / Q000378:metabolism; D013312:Stress, Physiological; D057177:TDP-43 Proteinopathies / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology
chemical_list: D004268:DNA-Binding Proteins; D012333:RNA, Messenger