Acta Neuropathologica: Exosome-induced lysosome permeability as a way for exosome tau seeds to escape to cytosomes

Neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), FTLD tau and amyotrophic lateral sclerosis (ALS) are all protein diseases characterized by misfolding and aggregation of signaling proteins.
AD is the most common form of Alzheimer's disease, in which extracellular amyloid plaques are formed by fibrous amyloid β peptides, while the microtubulin-related protein tau forms an internal deposit of nerve fibers called nerve fiber entanglements.
-tube-related protein tau plays a key role in AD and other tau diseases.
pathological mechanism in the progression of tau disease is the cross-synact diffusion of tau seeds, which works on secretion nano-vesicles produced by late-stage endocrine.
previous studies have shown that brain-induced exosome-wrapped tau seeds isolated from tau genetically modified rTg4510 mice can induce tau to aggregate in the affected cells.
addition, exosomes can hijack the introphy pathway, which transmits neurons through interconnected cells.
This paper mainly reveals how tau seeds contained in exosomes use lysosome degradation mechanisms to escape the connotation and induce tau to congreate in cytosytes in "tau biosensor cells" derived from HEK293T.
study found that most exosomes containing the connotations merge with lysosomes to form endosomes.
whether the presence of tau seeds or exosomes originated in the mouse brain or HEK293T cells, exosomes induced their permeability.
also found that permeability is a conservative mechanism that works in both non-neuron tau biosensors and primary neurons.
, however, the permeability of the inner lysosome occurs in only a small number of cells, which supports the idea that permeability occurs through the threshold mechanism.
interesting thing is that tau aggregation is induced only in permeable cells, which manifests it as an escape route for exosome tau seeds to enter the cytostyrine.
overexploitation of RAB7 is necessary to form an endosome, which strongly increases the aggregation of tau.
, tau aggregation can be reduced by inhibiting lysosome function with alkalinizers or by knocking out RAB7.
in general, the enzyme activity of lysosomes enhances the permeability of exosomes and endosome membranes, thus promoting the proximity of exosome tau seeds to cytostic tau to induce their aggregation.
of this paper emphasizes the importance of the intrinsic membrane integrity in the cell invasion mechanism of the misfolded protein that resists lysosome degradation.
Polanco, J.C., Hand, G.R., Briner, A. et al. Exosomes induce endolysosomal permeabilization as a gateway by which exosomal tau seeds escape into the cytosol. Acta Neuropathol (2021). MedSci Original Source: MedSci Original Copyright Notice: All text, images and audio and video materials on this website that indicate "Source: Mets Medicine" or "Source: MedSci Original" are owned by Mets Medicine and are not authorized to be reproduced by any media, website or individual, and are authorized to be reproduced with the words "Source: Mets Medicine".
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