PMID- 36367657
OWN - NLM
STAT- MEDLINE
DCOM- 20230125
LR  - 20230125
IS  - 1559-1182 (Electronic)
IS  - 0893-7648 (Print)
IS  - 0893-7648 (Linking)
VI  - 60
IP  - 2
DP  - 2023 Feb
TI  - Protein Expression of Amino Acid Transporters Is Altered in Isolated Cerebral 
      Microvessels of 5xFAD Mouse Model of Alzheimer's Disease.
PG  - 732-748
LID - 10.1007/s12035-022-03111-y [doi]
AB  - Membrane transporters such as ATP-binding cassette (ABC) and solute carrier (SLC) 
      transporters expressed at the neurovascular unit (NVU) play an important role in 
      drug delivery to the brain and have been demonstrated to be involved in 
      Alzheimer's disease (AD) pathogenesis. However, our knowledge of quantitative 
      changes in transporter absolute protein expression and functionality in vivo in 
      NVU in AD patients and animal models is limited. The study aim was to investigate 
      alterations in protein expression of ABC and SLC transporters in the isolated 
      brain microvessels and brain prefrontal cortices of a widely used model of 
      familial AD, 5xFAD mice (8 months old), using a sensitive liquid chromatography 
      tandem mass spectrometry-based quantitative targeted absolute proteomic approach. 
      Moreover, we examined alterations in brain prefrontal cortical and plasmatic 
      levels of transporter substrates in 5xFAD mice compared to age-matched wild-type 
      (WT) controls. ASCT1 (encoded by Slc1a4) protein expression in the isolated brain 
      microvessels and brain prefrontal cortices of 5xFAD mice was twice higher 
      compared to WT controls (p = 0.01). Brain cortical levels of ASCT1 substrate, 
      serine, were increased in 5xFAD mice compared to WT animals. LAT1 (encoded by 
      Slc7a5) and 4F2hc (encoded by Slc3a2) protein expressions were significantly 
      altered in the isolated brain microvessels of 5xFAD mice compared to WT controls 
      (p = 0.008 and p = 0.05, respectively). Overall, the study provides important 
      information, which is crucial for the optimal use of the 5xFAD mouse model in AD 
      drug development and for investigating novel drug delivery approaches. In 
      addition, the findings of the study shed light on the novel potential mechanisms 
      underlying AD pathogenesis.
CI  - (c) 2022. The Author(s).
FAU - Puris, Elena
AU  - Puris E
AUID- ORCID: 0000-0002-1769-389X
AD  - Institute of Pharmacy and Molecular Biotechnology, Ruprecht-Karls-University, Im 
      Neuenheimer Feld 329, 69120, Heidelberg, Germany. elena.puris@uni-heidelberg.de.
FAU - Saveleva, Liudmila
AU  - Saveleva L
AD  - A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 
      P.O. Box 1627, 70211, Kuopio, Finland.
FAU - de Sousa Maciel, Izaque
AU  - de Sousa Maciel I
AD  - A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 
      P.O. Box 1627, 70211, Kuopio, Finland.
FAU - Kanninen, Katja M
AU  - Kanninen KM
AD  - A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 
      P.O. Box 1627, 70211, Kuopio, Finland.
FAU - Auriola, Seppo
AU  - Auriola S
AD  - School of Pharmacy, University of Eastern Finland, P.O. Box 1627, 70211, Kuopio, 
      Finland.
FAU - Fricker, Gert
AU  - Fricker G
AD  - Institute of Pharmacy and Molecular Biotechnology, Ruprecht-Karls-University, Im 
      Neuenheimer Feld 329, 69120, Heidelberg, Germany.
LA  - eng
PT  - Journal Article
DEP - 20221111
PL  - United States
TA  - Mol Neurobiol
JT  - Molecular neurobiology
JID - 8900963
RN  - 0 (Amino Acid Transport Systems)
RN  - 0 (Slc1a4 protein, mouse)
RN  - 0 (Slc7a7 protein, mouse)
RN  - 0 (Slc3A2 protein, mouse)
SB  - IM
MH  - Animals
MH  - Mice
MH  - *Alzheimer Disease/pathology
MH  - Amino Acid Transport Systems/metabolism
MH  - Brain/metabolism
MH  - Disease Models, Animal
MH  - Mice, Transgenic
MH  - Microvessels/pathology
MH  - Proteomics/methods
PMC - PMC9849299
OTO - NOTNLM
OT  - 5xFAD mice
OT  - Alzheimer's disease
OT  - Amino acids
OT  - Brain cortex
OT  - Brain microvessels
OT  - Membrane transporter
COIS- The authors declare no competing interests.
EDAT- 2022/11/12 06:00
MHDA- 2023/01/21 06:00
PMCR- 2022/11/11
CRDT- 2022/11/11 11:18
PHST- 2022/07/19 00:00 [received]
PHST- 2022/10/26 00:00 [accepted]
PHST- 2022/11/12 06:00 [pubmed]
PHST- 2023/01/21 06:00 [medline]
PHST- 2022/11/11 11:18 [entrez]
PHST- 2022/11/11 00:00 [pmc-release]
AID - 10.1007/s12035-022-03111-y [pii]
AID - 3111 [pii]
AID - 10.1007/s12035-022-03111-y [doi]
PST - ppublish
SO  - Mol Neurobiol. 2023 Feb;60(2):732-748. doi: 10.1007/s12035-022-03111-y. Epub 2022 
      Nov 11.