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dc.contributor.authorBaskakov, Ilia V.
dc.date.accessioned2021-02-08T18:20:42Z
dc.date.available2021-02-08T18:20:42Z
dc.date.issued2021-01-18
dc.identifier.urihttp://hdl.handle.net/10713/14506
dc.description.abstractA number of neurodegenerative diseases including prion diseases, tauopathies and synu-cleinopathies exhibit multiple clinical phenotypes. A diversity of clinical phenotypes has been attributed to the ability of amyloidogenic proteins associated with a particular disease to acquire multiple, conformationally distinct, self-replicating states referred to as strains. Structural diversity of strains formed by tau, α-synuclein or prion proteins has been well documented. However, the question how different strains formed by the same protein elicit different clinical phenotypes remains poorly understood. The current article reviews emerging evidence suggesting that posttranslational modifications are important players in defining strain-specific structures and disease phenotypes. This article put forward a new hypothesis referred to as substrate selection hypothesis, according to which individual strains selectively recruit protein isoforms with a subset of posttranslational modifications that fit into strain-specific structures. Moreover, it is proposed that as a result of selective recruitment, strain-specific patterns of posttranslational modifications are formed, giving rise to unique disease phenotypes. Future studies should define whether cell-, region-and age-specific differences in metabolism of posttranslational modifications play a causative role in dictating strain identity and structural diversity of strains of sporadic origin. © 2021 by the author.en_US
dc.description.urihttps://doi.org/10.3390/ijms22020901en_US
dc.publisherMDPI AGen_US
dc.relation.ispartofInternational Journal of Molecular Sciencesen_US
dc.subjectAlzheimer’s diseasesen_US
dc.subjectN-linked glycansen_US
dc.subjectNeurodegenerative diseasesen_US
dc.subjectParkinson’s diseaseen_US
dc.subjectPhosphory-lationen_US
dc.subjectPosttranslational modificationsen_US
dc.subjectPrion diseaseen_US
dc.subjectPrion proteinen_US
dc.subjectStrainsen_US
dc.subjectTauen_US
dc.subjectUbiquitinationen_US
dc.subjectα-synucleinen_US
dc.titleFrom posttranslational modifications to disease phenotype: A substrate selection hypothesis in neurodegenerative diseasesen_US
dc.typeArticleen_US
dc.identifier.doi10.3390/ijms22020901
dc.source.volume22
dc.source.issue2
dc.source.beginpage1
dc.source.endpage12


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