Inherited and Sporadic Amyotrophic Lateral Sclerosis and Fronto-Temporal Lobar Degenerations arising from Pathological Condensates of Phase Separating Proteins.
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Peer-reviewed
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Abstract
Recent work on the biophysics of proteins with low complexity, intrinsically disordered domains that have the capacity to form biological condensates has profoundly altered the concepts about the pathogenesis of inherited and sporadic neurodegenerative disorders associated with pathological accumulation of these proteins. In the present review, we use the FUS, TDP-43 and A11 proteins as examples to illustrate how missense mutations and aberrant post-translational modifications of these proteins cause amyotrophic lateral sclerosis (ALS) and fronto-temporal lobar degeneration (FTLD).
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Keywords
ANXA11, Amyotrophic lateral sclerosis, FUS, TDP-43, biological condensates, fronto-temporal dementia, gelation, hydrogels, local RNA translation, neuronal transport granules, phase separation, stress granules, Amyotrophic Lateral Sclerosis, Annexins, Biological Transport, DNA-Binding Proteins, Frontotemporal Lobar Degeneration, Humans, Intracellular Membranes, Mutation, Missense, Neurodegenerative Diseases, Neurons, Protein Processing, Post-Translational, RNA-Binding Protein FUS, Temporal Lobe
Journal Title
Hum Mol Genet
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Journal ISSN
0964-6906
1460-2083
1460-2083
Volume Title
28
Publisher
Oxford University Press (OUP)
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All rights reserved
Sponsorship
Wellcome Trust (203249/Z/16/Z)
Supported by Canadian Institutes of Health Research, Wellcome Trust, Zenith Award from the US Alzheimer Society, ALS Society of Canada/Brain Canada.