Year: 2026
Type: article
Abstract: Tauopathies are a class of neurodegenerative diseases characterized by the accumulation of hyperphosphorylated, misfolded and aggregated Tau proteins and by dysfunctions in the autophagy-lysosome system. Whether the latter are a cause or a consequence of the former is unclear. The answer may come from a recent study by Mirfakhar et al. Using human iPSC-derived neurons harboring the MAPT p.R406W mutation in Tau, they were able to show that pathogenic Tau is able to broadly impair lysosomal function ahead of Tau accumulation. They also show that the degradative function of lysosomes, but not their motility, can be restored through pharmacological activation of autophagy, leading to reduced Tau levels. This work opens new therapeutic opportunities to eliminate early-on pathological misfolded Tau proteins before they can engage in a vicious cycle of aggregation, amplification and propagation.
Source: Traffic
DOI: 10.1111/tra.70051
Authors: Anaïs Bécot, Mehdi Kabani
Institutions: Inserm, Université Paris-Saclay
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,650
OpenAlex ID: W7210284616