Aging Cell
Bio@SNS, Scuola Normale Superiore, Pisa, Italy.
Published: January 2022
Frontotemporal dementia and amyotrophic lateral sclerosis are fatal and incurable neurodegenerative diseases linked to the pathological aggregation of the TDP-43 protein. This is an essential DNA/RNA-binding protein involved in transcription regulation, pre-RNA processing, and RNA transport. Having suitable animal models to study the mechanisms of TDP-43 aggregation is crucial to develop treatments against disease. We have previously demonstrated that the killifish Nothobranchius furzeri offers the advantage of being the shortest-lived vertebrate with a clear aging phenotype. Here, we show that the two N. furzeri paralogs of TDP-43 share high sequence homology with the human protein and recapitulate its cellular and biophysical behavior. During aging, N. furzeri TDP-43 spontaneously forms insoluble intracellular aggregates with amyloid characteristics and colocalizes with stress granules. Our results propose this organism as a valuable new model of TDP-43-related pathologies making it a powerful tool for the study of disease mechanism.
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http://dx.doi.org/10.1111/acel.13517 | DOI Listing |
Handb Clin Neurol
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Division of Neurology V-Neuropathology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
Alzheimer's disease (AD) is the most common disorder associated with cognitive impairment. Recent observations emphasize the pathogenic role of multiple factors inside and outside the central nervous system, supporting the notion that AD is a syndrome of many etiologies rather than a "heterogeneous" but ultimately unifying disease entity. Moreover, the defining pathology of amyloid and tau coexists with many others, such as α-synuclein, TDP-43, and others, as a rule, not an exception.
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Aging Cell
January 2022
Bio@SNS, Scuola Normale Superiore, Pisa, Italy.
Frontotemporal dementia and amyotrophic lateral sclerosis are fatal and incurable neurodegenerative diseases linked to the pathological aggregation of the TDP-43 protein. This is an essential DNA/RNA-binding protein involved in transcription regulation, pre-RNA processing, and RNA transport. Having suitable animal models to study the mechanisms of TDP-43 aggregation is crucial to develop treatments against disease.
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Department of Pharmacology and Chemical Biology, Emory University, School of Medicine, Atlanta 30322, Georgia; Center for Neurodegenerative Disease, Emory University, School of Medicine, Atlanta 30322, Georgia; Department of Neurology, Emory University, School of Medicine, Atlanta 30322, Georgia. Electronic address:
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University of Debrecen, Faculty of Medicine, Institute of Pathology, Division of Neuropathology, 4032 Debrecen, Nagyerdei krt. 98. Tel.: + 36 52 255-248.
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