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Degradation and Transmission of Tau by Autophagic-Endolysosomal Networks and Potential Therapeutic Targets for Tauopathy
Jiang S, Bhaskar K.. Frontiers in molecular neuroscience, 2020-10-16
Topic: Brain proteins, microglia and lab models
Tauopathies are a class of neurodegenerative diseases, including Alzheimer's disease (AD), Frontotemporal Dementia (FTD), Progressive Supranuclear Palsy (PSP), Corticobasal Degeneration (CBD), and many others where microtubule-associated protein tau (MAPT or tau) is hyperphosphorylated and aggregated to form insoluble paired helical filaments (PHFs) and ultimately neurofibrillary tangles (NFTs). Autophagic-endolysosomal networks (AELN) play important roles in tau clearance. Excessive soluble neurotoxic forms of tau and tau hyperphosphorylated at specific sites are cleared through the ubiquitin-proteasome system (UPS), Chaperon-mediated Autophagy (CMA), and endosomal microautophagy (e-MI). On the other hand, intra-neuronal insoluble tau aggregates are often degraded within lysosomes by macroautophagy. AELN defects have been observed in AD, FTD, CBD, and PSP, and lysosomal dysfunction was shown to promote the cleavage and neurotoxicity of tau. Moreover, several AD risk genes (e.g., PICALM , GRN , and BIN1 ) have been associated with dysregulation of AELN in the late-onset sporadic AD. Conversely, tau dissociation from microtubules interferes with retrograde transport of autophagosomes to lysosomes, and that tau fragments can also lead to lysosomal dysfunction. Recent studies suggest that tau is not merely an intra-neuronal protein, but it can be released to brain parenchyma via extracellular vesicles, like exosomes and ectosomes, and thus spread between neurons. Extracellular tau can also be taken up by microglial cells and astrocytes, either being degraded through AELN or propagated via exosomes. This article reviews the complex roles of AELN in the degradation and transmission of tau, potential diagnostic/therapeutic targets and strategies based on AELN-mediated tau clearance and propagation, and the current state of drug development targeting AELN and tau against tauopathies.
Key findings
- Moreover, several AD risk genes (e.g., PICALM , GRN , and BIN1 ) have been associated with dysregulation of AELN in the late-onset sporadic AD.
- Recent studies suggest that tau is not merely an intra-neuronal protein, but it can be released to brain parenchyma via extracellular vesicles, like exosomes and ectosomes, and thus spread between neurons.
Study details
- Evidence strengthLow
How this study scored 41/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 24 of the 58 points we could judge it on, which is 41 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Frontiers in molecular neuroscience) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2020 — within 10 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 33177989) |
| Free to read | 2 / 2 | Free to read |
| Points | 24 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 24 of the 58 points we could judge it on is 41 out of 100. |
| Total | 41 / 100 | — |
What each of these 20 components measures, and what this score is not →
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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APA 7th
Jiang, S., & Bhaskar, K. (2020). Degradation and Transmission of Tau by Autophagic-Endolysosomal Networks and Potential Therapeutic Targets for Tauopathy. Frontiers in molecular neuroscience. https://doi.org/10.3389/fnmol.2020.586731
Vancouver
Jiang S, Bhaskar K. Degradation and Transmission of Tau by Autophagic-Endolysosomal Networks and Potential Therapeutic Targets for Tauopathy. Frontiers in molecular neuroscience. 2020. doi:10.3389/fnmol.2020.586731. PMID: 33177989.
BibTeX
@article{jiang2020-33177989,
author = {Jiang, S. and Bhaskar, K.},
title = {{Degradation and Transmission of Tau by Autophagic-Endolysosomal Networks and Potential Therapeutic Targets for Tauopathy}},
journal = {Frontiers in molecular neuroscience},
year = {2020},
doi = {10.3389/fnmol.2020.586731},
pmid = {33177989},
url = {https://doi.org/10.3389/fnmol.2020.586731}
}
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