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 α‐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. (shrink)

The question of form in Peirce’s early thought constitutes the starting point of his reflection on the connection models of the parts of continua. I will show how, interpreted as reason rather than as cause, form becomes a productive event. In this productive event the form, as “condition of possibility of the relation of the elementary parts of representation” becomes a modeling dynamic which, starting from interpretation, allows initiation of the process of the passage from substance to being. The problem (...) of this passage is the problem of a continuity that cannot be thought by the classical linear model of time. (shrink)