PT  - JOURNAL ARTICLE
AU  - Eva Maria Johanna de Boer
AU  - Viyanti K Orie
AU  - Timothy Williams
AU  - Mark R Baker
AU  - Hugo M De Oliveira
AU  - Tuomo Polvikoski
AU  - Matthew Silsby
AU  - Parvathi Menon
AU  - Mehdi van den Bos
AU  - Glenda M Halliday
AU  - Leonard H van den Berg
AU  - Ludo Van Den Bosch
AU  - Philip van Damme
AU  - Matthew C Kiernan
AU  - Michael A van Es
AU  - Steve Vucic
TI  - TDP-43 proteinopathies: a new wave of neurodegenerative diseases
AID  - 10.1136/jnnp-2020-322983
DP  - 2021 Jan 01
TA  - Journal of Neurology, Neurosurgery & Psychiatry
PG  - 86--95
VI  - 92
IP  - 1
4099  - http://jnnp.bmj.com/content/92/1/86.short
4100  - http://jnnp.bmj.com/content/92/1/86.full
SO  - J Neurol Neurosurg Psychiatry2021 Jan 01; 92
AB  - Inclusions of pathogenic deposits containing TAR DNA-binding protein 43 (TDP-43) are evident in the brain and spinal cord of patients that present across a spectrum of neurodegenerative diseases. For instance, the majority of patients with sporadic amyotrophic lateral sclerosis (up to 97%) and a substantial proportion of patients with frontotemporal lobar degeneration (~45%) exhibit TDP-43 positive neuronal inclusions, suggesting a role for this protein in disease pathogenesis. In addition, TDP-43 inclusions are evident in familial ALS phenotypes linked to multiple gene mutations including the TDP-43 gene coding (TARDBP) and unrelated genes (eg, C9orf72). While TDP-43 is an essential RNA/DNA binding protein critical for RNA-related metabolism, determining the pathophysiological mechanisms through which TDP-43 mediates neurodegeneration appears complex, and unravelling these molecular processes seems critical for the development of effective therapies. This review highlights the key physiological functions of the TDP-43 protein, while considering an expanding spectrum of neurodegenerative diseases associated with pathogenic TDP-43 deposition, and dissecting key molecular pathways through which TDP-43 may mediate neurodegeneration.