PMID- 30562574
OWN - NLM
STAT- MEDLINE
DCOM- 20190411
LR  - 20201209
IS  - 1095-9327 (Electronic)
IS  - 1044-7431 (Linking)
VI  - 95
DP  - 2019 Mar
TI  - Impairment of chaperone-mediated autophagy affects neuronal homeostasis through 
      altered expression of DJ-1 and CRMP-2 proteins.
PG  - 1-12
LID - S1044-7431(18)30182-9 [pii]
LID - 10.1016/j.mcn.2018.12.006 [doi]
AB  - Chaperone-mediated autophagy (CMA) is a substrate-specific mode of lysosomal 
      proteolysis, with multiple lines of evidence connecting its dysfunction to both 
      ageing and disease. We have recently shown that CMA impairment through knock-down 
      of the lysosomal receptor LAMP2A is detrimental to neuronal viability in vivo; 
      however, it is not clear which subset of proteins regulated by the CMA pathway 
      mediate such changes. In this study, we have manipulated CMA function through 
      alterations of LAMP2A abundance in primary rat cortical neurons, to identify 
      potential changes to the neuronal proteome occurring prior to neurotoxic effects. 
      We have identified a list of proteins with significant, >2-fold change in 
      abundance following our manipulations, of which PARK7/DJ-1 - an anti-oxidant 
      implicated in hereditary forms of Parkinson's Disease (PD), and DPYSL2/CRMP-2 - a 
      microtubule-binding phosphoprotein involved in schizophrenia pathogenesis - were 
      both found to have measurable effects on neuronal homeostasis and phenotype. 
      Taken together, this study describes alterations in the abundance of neuronal 
      proteins involved in neuropsychiatric disorders upon CMA manipulation, and 
      suggests that such alterations may in part be responsible for the 
      neurodegeneration observed upon CMA impairment in vivo.
CI  - Copyright (c) 2018 Elsevier Inc. All rights reserved.
FAU - Brekk, Oeystein Roed
AU  - Brekk OR
AD  - Center of Clinical Research, Experimental Surgery and Translational Research, 
      Biomedical Research Foundation, Academy of Athens, Athens, Greece; University of 
      Crete, School of Medicine, Heraklion, Crete, Greece. Electronic address: 
      obrekk@mclean.harvard.edu.
FAU - Makridakis, Manousos
AU  - Makridakis M
AD  - Biotechnology Division, Biomedical Research Foundation, Academy of Athens, 
      Athens, Greece.
FAU - Mavroeidi, Panagiota
AU  - Mavroeidi P
AD  - Center of Clinical Research, Experimental Surgery and Translational Research, 
      Biomedical Research Foundation, Academy of Athens, Athens, Greece.
FAU - Vlahou, Antonia
AU  - Vlahou A
AD  - Biotechnology Division, Biomedical Research Foundation, Academy of Athens, 
      Athens, Greece.
FAU - Xilouri, Maria
AU  - Xilouri M
AD  - Center of Clinical Research, Experimental Surgery and Translational Research, 
      Biomedical Research Foundation, Academy of Athens, Athens, Greece.
FAU - Stefanis, Leonidas
AU  - Stefanis L
AD  - Center of Clinical Research, Experimental Surgery and Translational Research, 
      Biomedical Research Foundation, Academy of Athens, Athens, Greece; Second 
      Department of Neurology, National and Kapodistrian University of Athens Medical 
      School, Athens, Greece. Electronic address: lstefanis@bioacademy.gr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20181215
PL  - United States
TA  - Mol Cell Neurosci
JT  - Molecular and cellular neurosciences
JID - 9100095
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Lysosomal-Associated Membrane Protein 2)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (collapsin response mediator protein-2)
RN  - EC 3.1.2.- (PARK7 protein, rat)
RN  - EC 3.1.2.- (Protein Deglycase DJ-1)
SB  - IM
MH  - Animals
MH  - *Autophagy
MH  - Cells, Cultured
MH  - Female
MH  - HEK293 Cells
MH  - *Homeostasis
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins
MH  - Lysosomal-Associated Membrane Protein 2/genetics/metabolism
MH  - Nerve Tissue Proteins/genetics/*metabolism
MH  - Neurons/*metabolism
MH  - Protein Deglycase DJ-1/genetics/*metabolism
MH  - Rats
MH  - Rats, Wistar
OTO - NOTNLM
OT  - Chaperone-mediated autophagy (CMA)
OT  - DPYSL2/CRMP-2
OT  - LAMP2A
OT  - PARK7/DJ-1
OT  - Parkinson's Disease (PD)
OT  - Proteomics
OT  - Schizophrenia
EDAT- 2018/12/19 06:00
MHDA- 2019/04/12 06:00
CRDT- 2018/12/19 06:00
PHST- 2018/06/13 00:00 [received]
PHST- 2018/11/20 00:00 [revised]
PHST- 2018/12/13 00:00 [accepted]
PHST- 2018/12/19 06:00 [pubmed]
PHST- 2019/04/12 06:00 [medline]
PHST- 2018/12/19 06:00 [entrez]
AID - S1044-7431(18)30182-9 [pii]
AID - 10.1016/j.mcn.2018.12.006 [doi]
PST - ppublish
SO  - Mol Cell Neurosci. 2019 Mar;95:1-12. doi: 10.1016/j.mcn.2018.12.006. Epub 2018 
      Dec 15.