Journal article
Molecular mechanisms underlying TDP-43 pathology in cellular and animal models of ALS and FTLD
International Journal of Molecular Sciences, Vol.22(9), Article 4705
2021
Abstract
Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are neurodegenerative disorders that exist on a disease spectrum due to pathological, clinical and genetic overlap. In up to 97% of ALS cases and ~50% of FTLD cases, the primary pathological protein observed in affected tissues is TDP-43, which is hyperphosphorylated, ubiquitinated and cleaved. The TDP-43 is observed in aggregates that are abnormally located in the cytoplasm. The pathogenicity of TDP-43 cytoplasmic aggregates may be linked with both a loss of nuclear function and a gain of toxic functions. The cellular processes involved in ALS and FTLD disease pathogenesis include changes to RNA splicing, abnormal stress granules, mitochondrial dysfunction, impairments to axonal transport and autophagy, abnormal neuromuscular junctions, endoplasmic reticulum stress and the subsequent induction of the unfolded protein response. Here, we review and discuss the evidence for alterations to these processes that have been reported in cellular and animal models of TDP-43 proteinopathy.
Details
- Title
- Molecular mechanisms underlying TDP-43 pathology in cellular and animal models of ALS and FTLD
- Authors/Creators
- A. Wood (Author/Creator) - Murdoch UniversityY. Gurfinkel (Author/Creator) - Murdoch UniversityN. Polain (Author/Creator) - Murdoch UniversityW. Lamont (Author/Creator) - Perron Institute for Neurological and Translational ScienceS.L. Rea (Author/Creator) - Murdoch University
- Publication Details
- International Journal of Molecular Sciences, Vol.22(9), Article 4705
- Publisher
- MDPI AG
- Identifiers
- 991005542746207891
- Copyright
- © 2021 The Authors
- Murdoch Affiliation
- Centre for Molecular Medicine and Innovative Therapeutics
- Language
- English
- Resource Type
- Journal article
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Source: InCites
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- Collaboration types
- Domestic collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.52 Neurodegenerative Diseases
- 1.52.765 ALS Mechanisms
- Web Of Science research areas
- Biochemistry & Molecular Biology
- Chemistry, Multidisciplinary
- ESI research areas
- Chemistry