TDP-43 and FUS in amyotrophic lateral sclerosis and frontotemporal dementia - PubMed (original) (raw)

Review

TDP-43 and FUS in amyotrophic lateral sclerosis and frontotemporal dementia

Ian Ra Mackenzie et al. Lancet Neurol. 2010 Oct.

Abstract

Abnormal intracellular protein aggregates comprise a key characteristic in most neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The seminal discoveries of accumulation of TDP-43 in most cases of ALS and the most frequent form of FTD, frontotemporal lobar degeneration with ubiquitinated inclusions, followed by identification of FUS as the novel pathological protein in a small subset of patients with ALS and various FTD subtypes provide clear evidence that these disorders are related. The creation of a novel molecular classification of ALS and FTD based on the identity of the predominant protein abnormality has, therefore, been possible. The striking functional and structural similarities of TDP-43 and FUS, which are both DNA/RNA binding proteins, imply that abnormal RNA metabolism is a pivotal event, but the mechanisms leading to TDP-43 and FUS accumulation and the resulting neurodegeneration are currently unknown. Nonetheless, TDP-43 and FUS are promising candidates for the development of novel biomarker assays and targeted therapies.

PubMed Disclaimer

Cited by

CK2 and protein kinases of the CK1 superfamily as targets for neurodegenerative disorders.
Baier A, Szyszka R. Baier A, et al. Front Mol Biosci. 2022 Oct 6;9:916063. doi: 10.3389/fmolb.2022.916063. eCollection 2022. Front Mol Biosci. 2022. PMID: 36275622 Free PMC article. Review.
The future of blood-based biomarkers for Alzheimer's disease.
Henriksen K, O'Bryant SE, Hampel H, Trojanowski JQ, Montine TJ, Jeromin A, Blennow K, Lönneborg A, Wyss-Coray T, Soares H, Bazenet C, Sjögren M, Hu W, Lovestone S, Karsdal MA, Weiner MW; Blood-Based Biomarker Interest Group. Henriksen K, et al. Alzheimers Dement. 2014 Jan;10(1):115-31. doi: 10.1016/j.jalz.2013.01.013. Epub 2013 Jul 11. Alzheimers Dement. 2014. PMID: 23850333 Free PMC article. Review.
Genetic Risk Factors for Essential Tremor: A Review.
Siokas V, Aloizou AM, Tsouris Z, Liampas I, Aslanidou P, Dastamani M, Brotis AG, Bogdanos DP, Hadjigeorgiou GM, Dardiotis E. Siokas V, et al. Tremor Other Hyperkinet Mov (N Y). 2020 Jun 11;10:4. doi: 10.5334/tohm.67. Tremor Other Hyperkinet Mov (N Y). 2020. PMID: 32775018 Free PMC article. Review.
The inhibition of TDP-43 mitochondrial localization blocks its neuronal toxicity.
Wang W, Wang L, Lu J, Siedlak SL, Fujioka H, Liang J, Jiang S, Ma X, Jiang Z, da Rocha EL, Sheng M, Choi H, Lerou PH, Li H, Wang X. Wang W, et al. Nat Med. 2016 Aug;22(8):869-78. doi: 10.1038/nm.4130. Epub 2016 Jun 27. Nat Med. 2016. PMID: 27348499 Free PMC article.
Aberrant localization of FUS and TDP43 is associated with misfolding of SOD1 in amyotrophic lateral sclerosis.
Pokrishevsky E, Grad LI, Yousefi M, Wang J, Mackenzie IR, Cashman NR. Pokrishevsky E, et al. PLoS One. 2012;7(4):e35050. doi: 10.1371/journal.pone.0035050. Epub 2012 Apr 6. PLoS One. 2012. PMID: 22493728 Free PMC article.

TDP-43 and FUS in amyotrophic lateral sclerosis and frontotemporal dementia - PubMed (original) (raw)