Mechanisms of secretion and spreading of pathological tau protein

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Brunello , C A , Merezhko , M , Uronen , R-L & Huttunen , H J 2020 , ' Mechanisms of secretion and spreading of pathological tau protein ' , Cellular and Molecular Life Sciences , vol. 77 , no. 9 , pp. 1721-1744 . https://doi.org/10.1007/s00018-019-03349-1

Title: Mechanisms of secretion and spreading of pathological tau protein
Author: Brunello, Cecilia A.; Merezhko, Maria; Uronen, Riikka-Liisa; Huttunen, Henri J.
Contributor: University of Helsinki, Neuroscience Center
University of Helsinki, Neuroscience Center
University of Helsinki, Neuroscience Center
University of Helsinki, Neuroscience Center
Date: 2020-05
Language: eng
Number of pages: 24
Belongs to series: Cellular and Molecular Life Sciences
ISSN: 1420-9071
URI: http://hdl.handle.net/10138/315264
Abstract: Accumulation of misfolded and aggregated forms of tau protein in the brain is a neuropathological hallmark of tauopathies, such as Alzheimer’s disease and frontotemporal lobar degeneration. Tau aggregates have the ability to transfer from one cell to another and to induce templated misfolding and aggregation of healthy tau molecules in previously healthy cells, thereby propagating tau pathology across different brain areas in a prion-like manner. The molecular mechanisms involved in cell-to-cell transfer of tau aggregates are diverse, not mutually exclusive and only partially understood. Intracellular accumulation of misfolded tau induces several mechanisms that aim to reduce the cellular burden of aggregated proteins and also promote secretion of tau aggregates. However, tau may also be released from cells physiologically unrelated to protein aggregation. Tau secretion involves multiple vesicular and non-vesicle-mediated pathways, including secretion directly through the plasma membrane. Consequently, extracellular tau can be found in various forms, both as a free protein and in vesicles, such as exosomes and ectosomes. Once in the extracellular space, tau aggregates can be internalized by neighboring cells, both neurons and glial cells, via endocytic, pinocytic and phagocytic mechanisms. Importantly, accumulating evidence suggests that prion-like propagation of misfolding protein pathology could provide a general mechanism for disease progression in tauopathies and other related neurodegenerative diseases. Here, we review the recent literature on cellular mechanisms involved in cell-to-cell transfer of tau, with a particular focus in tau secretion.
Subject: 3112 Neurosciences
Amyloid
Tau
Aggregation
Propagation
Prion
Unconventional protein secretion
Extracellular vesicles
PAIRED HELICAL FILAMENTS
NUCLEATED CONFORMATIONAL CONVERSION
HEPARAN-SULFATE PROTEOGLYCANS
ALZHEIMERS-DISEASE BIOMARKERS
ALPHA-SYNUCLEIN PATHOLOGY
EXOSOME-ASSOCIATED TAU
GROWTH-FACTOR 2
FRONTOTEMPORAL DEMENTIA
MICROTUBULE-BINDING
NEUROFIBRILLARY TANGLES
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