Altered Proteostasis in Neurodegenerative Tauopathies.
Adv Exp Med Biol
; 1233: 177-194, 2020.
Article
em En
| MEDLINE
| ID: mdl-32274757
ABSTRACT
Tauopathies are a heterogeneous group of neurodegenerative dementias involving perturbations in the levels, phosphorylation or mutations of the neuronal microtubule-binding protein Tau. Tauopathies are characterized by accumulation of hyperphosphorylated Tau leading to formation of a range of aggregates including macromolecular ensembles such as Paired Helical filaments and Neurofibrilary Tangles whose morphology characterizes and differentiates these disease states. Why nonphysiological Tau proteins elude the surveillance normal proteostatic mechanisms and eventually form these macromolecular assemblies is a central mostly unresolved question of cardinal importance for diagnoses and potential therapeutic interventions. We discuss the response of the Ubiquitin-Proteasome system, autophagy and the Endoplasmic Reticulum-Unfolded Protein response in Tauopathy models and patients, revealing interactions of components of these systems with Tau, but also of the effects of pathological Tau on these systems which eventually lead to Tau aggregation and accumulation. These interactions point to potential disease biomarkers and future potential therapeutic targets.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tauopatias
/
Proteostase
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Adv Exp Med Biol
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Grécia