PMID- 35883562
OWN - NLM
STAT- MEDLINE
DCOM- 20220728
LR  - 20220810
IS  - 2218-273X (Electronic)
IS  - 2218-273X (Linking)
VI  - 12
IP  - 7
DP  - 2022 Jul 20
TI  - Immunohistochemical Demonstration of the pGlu79 alpha-Synuclein Fragment in 
      Alzheimer's Disease and Its Tg2576 Mouse Model.
LID - 10.3390/biom12071006 [doi]
LID - 1006
AB  - The deposition of beta-amyloid peptides and of alpha-synuclein proteins is a 
      neuropathological hallmark in the brains of Alzheimer's disease (AD) and 
      Parkinson's disease (PD) subjects, respectively. However, there is accumulative 
      evidence that both proteins are not exclusive for their clinical entity but 
      instead co-exist and interact with each other. Here, we investigated the presence 
      of a newly identified, pyroglutamate79-modified alpha-synuclein variant 
      (pGlu79-aSyn)-along with the enzyme matrix metalloproteinase-3 (MMP-3) and 
      glutaminyl cyclase (QC) implicated in its formation-in AD and in the transgenic 
      Tg2576 AD mouse model. In the human brain, pGlu79-aSyn was detected in cortical 
      pyramidal neurons, with more distinct labeling in AD compared to control brain 
      tissue. Using immunohistochemical double and triple labelings and confocal laser 
      scanning microscopy, we demonstrate an association of pGlu79-aSyn, MMP-3 and QC 
      with beta-amyloid plaques. In addition, pGlu79-aSyn and QC were present in amyloid 
      plaque-associated reactive astrocytes that were also immunoreactive for the 
      chaperone heat shock protein 27 (HSP27). Our data are consistent for the 
      transgenic mouse model and the human clinical condition. We conclude that 
      pGlu79-aSyn can be generated extracellularly or within reactive astrocytes, 
      accumulates in proximity to beta-amyloid plaques and induces an astrocytic protein 
      unfolding mechanism involving HSP27.
FAU - Bluhm, Alexandra
AU  - Bluhm A
AD  - Paul Flechsig Institute for Brain Research, University of Leipzig, 04103 Leipzig, 
      Germany.
FAU - Schrempel, Sarah
AU  - Schrempel S
AD  - Paul Flechsig Institute for Brain Research, University of Leipzig, 04103 Leipzig, 
      Germany.
FAU - Schilling, Stephan
AU  - Schilling S
AD  - Fraunhofer Institute for Cell Therapy and Immunology, Department of Drug Design 
      and Target Validation, 06120 Halle (Saale), Germany.
AD  - Faculty of Applied Biosciences and Process Engineering, Anhalt University of 
      Applied Sciences, 06366 Kothen, Germany.
FAU - von Horsten, Stephan
AU  - von Horsten S
AUID- ORCID: 0000-0001-6409-0664
AD  - Department for Experimental Therapy, University Clinics Erlangen and Preclinical 
      Experimental Center, University of Erlangen-Nuremberg, 91054 Erlangen, Germany.
FAU - Schulze, Anja
AU  - Schulze A
AUID- ORCID: 0000-0002-3358-8299
AD  - Fraunhofer Institute for Cell Therapy and Immunology, Department of Drug Design 
      and Target Validation, 06120 Halle (Saale), Germany.
FAU - Rossner, Steffen
AU  - Rossner S
AD  - Paul Flechsig Institute for Brain Research, University of Leipzig, 04103 Leipzig, 
      Germany.
FAU - Hartlage-Rubsamen, Maike
AU  - Hartlage-Rubsamen M
AD  - Paul Flechsig Institute for Brain Research, University of Leipzig, 04103 Leipzig, 
      Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220720
PL  - Switzerland
TA  - Biomolecules
JT  - Biomolecules
JID - 101596414
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (HSP27 Heat-Shock Proteins)
RN  - 0 (alpha-Synuclein)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - *Alzheimer Disease/metabolism
MH  - Amyloid beta-Peptides/metabolism
MH  - Animals
MH  - Brain/metabolism
MH  - Disease Models, Animal
MH  - HSP27 Heat-Shock Proteins/metabolism
MH  - Humans
MH  - Matrix Metalloproteinase 3/metabolism
MH  - Mice
MH  - Mice, Transgenic
MH  - Plaque, Amyloid/metabolism/pathology
MH  - alpha-Synuclein/genetics/metabolism
PMC - PMC9312983
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - glutaminyl cyclase
OT  - heat shock protein 27
OT  - matrix metalloproteinase-3
OT  - reactive astrocytes
OT  - alpha-synuclein
OT  - beta-amyloid
COIS- The authors declare no conflict of interest.
EDAT- 2022/07/28 06:00
MHDA- 2022/07/29 06:00
PMCR- 2022/07/20
CRDT- 2022/07/27 01:06
PHST- 2022/05/27 00:00 [received]
PHST- 2022/07/14 00:00 [revised]
PHST- 2022/07/14 00:00 [accepted]
PHST- 2022/07/27 01:06 [entrez]
PHST- 2022/07/28 06:00 [pubmed]
PHST- 2022/07/29 06:00 [medline]
PHST- 2022/07/20 00:00 [pmc-release]
AID - biom12071006 [pii]
AID - biomolecules-12-01006 [pii]
AID - 10.3390/biom12071006 [doi]
PST - epublish
SO  - Biomolecules. 2022 Jul 20;12(7):1006. doi: 10.3390/biom12071006.