Home › Research › Disease mechanisms
The Mechanistic Link Between Tau-Driven Proteotoxic Stress and Cellular Senescence in Alzheimer's Disease
Karthikeyan Tangavelou, Kiran Bhaskar. International journal of molecular sciences, 2024-11-17
Topic: Disease mechanisms in lab and animal studies
In Alzheimer's disease (AD), tau dissociates from microtubules (MTs) due to hyperphosphorylation and misfolding. It is degraded by various mechanisms, including the 20S proteasome, chaperone-mediated autophagy (CMA), 26S proteasome, macroautophagy, and aggrephagy. Neurofibrillary tangles (NFTs) form upon the impairment of aggrephagy, and eventually, the ubiquitin chaperone valosin-containing protein (VCP) and heat shock 70 kDa protein (HSP70) are recruited to the sites of NFTs for the extraction of tau for the ubiquitin-proteasome system (UPS)-mediated degradation. However, the impairment of tau degradation in neurons allows tau to be secreted into the extracellular space. Secreted tau can be monomers, oligomers, and paired helical filaments (PHFs), which are seeding competent pathological tau that can be endocytosed/phagocytosed by healthy neurons, microglia, astrocytes, oligodendrocyte progenitor cells (OPCs), and oligodendrocytes, often causing proteotoxic stress and eventually triggers senescence. Senescent cells secrete various senescence-associated secretory phenotype (SASP) factors, which trigger cellular atrophy, causing decreased brain volume in human AD. However, the molecular mechanisms of proteotoxic stress and cellular senescence are not entirely understood and are an emerging area of research. Therefore, this comprehensive review summarizes pertinent studies that provided evidence for the sequential tau degradation, failure, and the mechanistic link between tau-driven proteotoxic stress and cellular senescence in AD.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Tangavelou, K., & Bhaskar, K. (2024). The Mechanistic Link Between Tau-Driven Proteotoxic Stress and Cellular Senescence in Alzheimer's Disease. International journal of molecular sciences. https://doi.org/10.3390/ijms252212335
Vancouver
Tangavelou K, Bhaskar K. The Mechanistic Link Between Tau-Driven Proteotoxic Stress and Cellular Senescence in Alzheimer's Disease. International journal of molecular sciences. 2024. doi:10.3390/ijms252212335. PMID: 39596399.
BibTeX
@article{tangavelou2024-39596399,
author = {Tangavelou, Karthikeyan and Bhaskar, Kiran},
title = {{The Mechanistic Link Between Tau-Driven Proteotoxic Stress and Cellular Senescence in Alzheimer's Disease}},
journal = {International journal of molecular sciences},
year = {2024},
doi = {10.3390/ijms252212335},
pmid = {39596399},
url = {https://doi.org/10.3390/ijms252212335}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
Key findings
- However, the impairment of tau degradation in neurons allows tau to be secreted into the extracellular space.
- Secreted tau can be monomers, oligomers, and paired helical filaments (PHFs), which are seeding competent pathological tau that can be endocytosed/phagocytosed by healthy neurons, microglia, astrocytes, oligodendrocyte progenitor cells (OPCs), and oligodendrocytes, often causing proteotoxic stress and eventually triggers senescence.
- Senescent cells secrete various senescence-associated secretory phenotype (SASP) factors, which trigger cellular atrophy, causing decreased brain volume in human AD.
- However, the molecular mechanisms of proteotoxic stress and cellular senescence are not entirely understood and are an emerging area of research.
- Therefore, this comprehensive review summarizes pertinent studies that provided evidence for the sequential tau degradation, failure, and the mechanistic link between tau-driven proteotoxic stress and cellular senescence in AD.
Study details
- Evidence strengthLow
How this study scored 43/100
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, multi-centre collaboration and free to read, so those were left out: it earned 24 of the 56 points we could judge it on, which is 43 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (International journal of molecular sciences) |
| 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 | 4 / 5 | 2024 — within 3 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 39596399) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 24 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 24 of the 56 points we could judge it on is 43 out of 100. |
| Total | 43 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Free copy unknown: no free-copy check has an answer for this record yet. That does not mean it is paywalled.
Related studies in Disease mechanisms
Also tagged “phosphorylation”
387 studies in the library carry the topic tag “phosphorylation”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 387 tagged studies.