“S‐Tau‐Lled” Lysosomes Disrupt Autophagic Processes in Neurodegeneration

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.

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BibTeX

@article{becot2026staulled,
  title = {{“S‐Tau‐Lled” Lysosomes Disrupt Autophagic Processes in Neurodegeneration}},
  author = {Anaïs Bécot and Mehdi Kabani},
  journal = {Traffic},
  year = {2026},
  month = sep,
  doi = {10.1111/tra.70051},
  url = {https://hal.science/hal-05740538v1},
  note = {CC BY 4.0},
}

RIS

TY  - JOUR
TI  - “S‐Tau‐Lled” Lysosomes Disrupt Autophagic Processes in Neurodegeneration
AU  - Anaïs Bécot
AU  - Mehdi Kabani
PY  - 2026
DA  - 2026/09/06
JO  - Traffic
DO  - 10.1111/tra.70051
UR  - https://hal.science/hal-05740538v1
AB  - 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.
SN  - 1398-9219
SN  - 1600-0854
ER  -

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