PMID- 30530923
OWN - NLM
STAT- MEDLINE
DCOM- 20191219
LR  - 20200309
IS  - 1945-4589 (Electronic)
IS  - 1945-4589 (Linking)
VI  - 10
IP  - 12
DP  - 2018 Dec 7
TI  - Caloric restriction rescues yeast cells from alpha-synuclein toxicity through 
      autophagic control of proteostasis.
PG  - 3821-3833
LID - 10.18632/aging.101675 [doi]
AB  - alpha-Synuclein (SNCA) is a presynaptic protein that is associated with the 
      pathophysiology of synucleinopathies, including Parkinson's disease. SNCA is a 
      naturally aggregation-prone protein, which may be degraded by the 
      ubiquitin-proteasome system (UPS) and by lysosomal degradation pathways. Besides 
      being a target of the proteolytic systems, SNCA can also alter the function of 
      these pathways further, contributing to the progression of neurodegeneration. 
      Deterioration of UPS and autophagy activities with aging further aggravates this 
      toxic cycle. Caloric restriction (CR) is still the most effective non-genetic 
      intervention promoting lifespan extension. It is known that CR-mediated lifespan 
      extension is linked to the regulation of proteolytic systems, but the mechanisms 
      underlying CR rescue of SNCA toxicity remain poorly understood. This study shows 
      that CR balances UPS and autophagy activities during aging. CR enhances UPS 
      activity, reversing the decline of the UPS activity promoted by SNCA, and keeps 
      autophagy at homeostatic levels. Maintenance of autophagy at homeostatic levels 
      appears to be relevant for UPS activity and for the mechanism underlying rescue 
      of cells from SNCA-mediated toxicity by CR.
FAU - Sampaio-Marques, Belem
AU  - Sampaio-Marques B
AD  - Life and Health Sciences Research Institute (ICVS), School of Medicine, 
      University of Minho, Braga, Portugal.
AD  - ICVS/3B's - PT Government Associate Laboratory, Braga/Guimaraes, University of 
      Minho, Braga, Portugal.
FAU - Pereira, Helder
AU  - Pereira H
AD  - Life and Health Sciences Research Institute (ICVS), School of Medicine, 
      University of Minho, Braga, Portugal.
AD  - ICVS/3B's - PT Government Associate Laboratory, Braga/Guimaraes, University of 
      Minho, Braga, Portugal.
FAU - Santos, Ana R
AU  - Santos AR
AD  - Life and Health Sciences Research Institute (ICVS), School of Medicine, 
      University of Minho, Braga, Portugal.
AD  - ICVS/3B's - PT Government Associate Laboratory, Braga/Guimaraes, University of 
      Minho, Braga, Portugal.
FAU - Teixeira, Alexandra
AU  - Teixeira A
AD  - Life and Health Sciences Research Institute (ICVS), School of Medicine, 
      University of Minho, Braga, Portugal.
AD  - ICVS/3B's - PT Government Associate Laboratory, Braga/Guimaraes, University of 
      Minho, Braga, Portugal.
FAU - Ludovico, Paula
AU  - Ludovico P
AD  - Life and Health Sciences Research Institute (ICVS), School of Medicine, 
      University of Minho, Braga, Portugal.
AD  - ICVS/3B's - PT Government Associate Laboratory, Braga/Guimaraes, University of 
      Minho, Braga, Portugal.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Aging (Albany NY)
JT  - Aging
JID - 101508617
RN  - 0 (Fungal Proteins)
RN  - 0 (alpha-Synuclein)
SB  - IM
MH  - Autophagy/*physiology
MH  - *Caloric Restriction
MH  - Fungal Proteins/genetics/*metabolism
MH  - Gene Expression Regulation, Fungal/physiology
MH  - Humans
MH  - Yeasts/genetics/*physiology
MH  - alpha-Synuclein/*metabolism
PMC - PMC6326672
OTO - NOTNLM
OT  - aging
OT  - alpha-synuclein
OT  - autophagy
OT  - caloric restriction
OT  - ubiquitin-proteasome system
COIS- CONFLICTS OF INTEREST: The authors report no conflicts of interest in this work.
EDAT- 2018/12/12 06:00
MHDA- 2019/12/20 06:00
PMCR- 2018/12/01
CRDT- 2018/12/12 06:00
PHST- 2018/05/04 00:00 [received]
PHST- 2018/11/18 00:00 [accepted]
PHST- 2018/12/12 06:00 [pubmed]
PHST- 2019/12/20 06:00 [medline]
PHST- 2018/12/12 06:00 [entrez]
PHST- 2018/12/01 00:00 [pmc-release]
AID - 101675 [pii]
AID - 10.18632/aging.101675 [doi]
PST - ppublish
SO  - Aging (Albany NY). 2018 Dec 7;10(12):3821-3833. doi: 10.18632/aging.101675.