The chaperone Clusterin in neurodegeneration-friend or foe?

Yuste-Checa, Patricia; Bracher, Andreas und Hartl, F. Ulrich (2022): The chaperone Clusterin in neurodegeneration-friend or foe? In: Bioessays, Bd. 44, Nr. 7, e2100287

Abstract

Fibrillar protein aggregates are the pathological hallmark of a group of age-dependent neurodegenerative conditions, including Alzheimer's and Parkinson's disease. Aggregates of the microtubule-associated protein Tau are observed in Alzheimer's disease and primary tauopathies. Tau pathology propagates from cell to cell in a prion-like process that is likely subject to modulation by extracellular chaperones such as Clusterin. We recently reported that Clusterin delayed Tau fibril formation but enhanced the activity of Tau oligomers to seed aggregation of endogenous Tau in a cellular model. In contrast, Clusterin inhibited the propagation of alpha-Synuclein aggregates associated with Parkinson's disease. These findings raise the possibility of a mechanistic link between Clusterin upregulation observed in Alzheimer's disease and the progression of Tau pathology. Here we review the diverse functions of Clusterin in the pathogenesis of neurodegenerative diseases, focusing on evidence that Clusterin may act either as a suppressor or enhancer of pathology.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin > Munich Cluster for Systems Neurology (SyNergy)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198