PMID- 38125374
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231222
VI  - 4
IP  - 4
DP  - 2023
TI  - Emerging evidence for dysregulated proteome cargoes of tau-propagating 
      extracellular vesicles driven by familial mutations of tau and presenilin.
PG  - 588-598
LID - 10.20517/evcna.2023.44 [doi]
AB  - Tau propagation, pathogenesis, and neurotoxicity are hallmarks of 
      neurodegenerative diseases that result in cognitive impairment. Tau accumulates 
      in Alzheimer's disease (AD), frontotemporal dementia and parkinsonism linked to 
      chromosome 17 (FTDP-17), chronic traumatic encephalopathy (CTE), progressive 
      supranuclear palsy, and related tauopathies. Knowledge of the mechanisms for tau 
      propagation in neurodegeneration is necessary for understanding the development 
      of dementia. Exosomes, known as extracellular vesicles (EVs), have emerged as 
      participants in promoting tau propagation. Recent findings show that EVs 
      generated by neurons expressing familial mutations of tauopathies of FTDP-17 
      (P301L and V337M) (mTau) and presenilin (A246E) (mPS1) in AD induce tau 
      propagation and accumulation after injection into rodent brain. To gain knowledge 
      of the proteome cargoes of the mTau and mPS1 EVs that promote tau pathogenesis, 
      this review compares the proteomes of these EVs, which results in important new 
      questions concerning EV mechanisms of tau pathogenesis. Proteomics data show that 
      EVs produced by mTau- and mPS1-expressing iPSC neurons share proteins involved in 
      exocytosis and vesicle secretion and, notably, these EVs also possess differences 
      in protein components of vesicle-mediated transport, extracellular functions, and 
      cell adhesion. It will be important for future studies to gain an understanding 
      of the breadth of familial genetic mutations of tau, presenilin, and other genes 
      in promoting EV initiation of tau propagation and pathogenesis. Furthermore, 
      elucidation of EV cargo components that mediate tau propagation will have 
      potential as biomarkers and therapeutic strategies to ameliorate dementia of 
      tauopathies.
FAU - Hook, Vivian
AU  - Hook V
AD  - Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, 
      San Diego, CA 92093, USA.
AD  - Department of Neurosciences, University of California, San Diego, CA 92093, USA.
FAU - Podvin, Sonia
AU  - Podvin S
AD  - Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, 
      San Diego, CA 92093, USA.
FAU - Mosier, Charles
AU  - Mosier C
AD  - Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, 
      San Diego, CA 92093, USA.
FAU - Boyarko, Ben
AU  - Boyarko B
AD  - Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, 
      San Diego, CA 92093, USA.
FAU - Seyffert, Laura
AU  - Seyffert L
AD  - Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, 
      San Diego, CA 92093, USA.
FAU - Stringer, Haley
AU  - Stringer H
AD  - Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, 
      San Diego, CA 92093, USA.
FAU - Rissman, Robert A
AU  - Rissman RA
AD  - Department of Neurosciences, University of California, San Diego, CA 92093, USA.
AD  - Veterans Affairs San Diego Health System, San Diego, CA 92093, USA.
LA  - eng
GR  - R01 NS109075/NS/NINDS NIH HHS/United States
GR  - R56 AG057469/AG/NIA NIH HHS/United States
PT  - Journal Article
DEP - 20231121
PL  - United States
TA  - Extracell Vesicles Circ Nucl Acids
JT  - Extracellular vesicles and circulating nucleic acids
JID - 101775065
PMC - PMC10732590
MID - NIHMS1946879
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - Tauopathies
OT  - exosome
OT  - extracellular vesicle
OT  - frontotemporal dementia
OT  - mutant presenilin
OT  - mutant tau
OT  - proteomics
COIS- Conflicts of interest The authors declared that there are no conflicts of 
      interest.
EDAT- 2023/12/21 06:42
MHDA- 2023/12/21 06:43
PMCR- 2023/12/20
CRDT- 2023/12/21 04:12
PHST- 2023/12/21 06:43 [medline]
PHST- 2023/12/21 06:42 [pubmed]
PHST- 2023/12/21 04:12 [entrez]
PHST- 2023/12/20 00:00 [pmc-release]
AID - 10.20517/evcna.2023.44 [doi]
PST - ppublish
SO  - Extracell Vesicles Circ Nucl Acids. 2023;4(4):588-598. doi: 
      10.20517/evcna.2023.44. Epub 2023 Nov 21.