PMID- 27109470
OWN - NLM
STAT- MEDLINE
DCOM- 20170810
LR  - 20201209
IS  - 1872-6216 (Electronic)
IS  - 0047-6374 (Linking)
VI  - 161
IP  - Pt B
DP  - 2017 Jan
TI  - Caloric restriction alleviates alpha-synuclein toxicity in aged yeast cells by 
      controlling the opposite roles of Tor1 and Sir2 on autophagy.
PG  - 270-276
LID - S0047-6374(16)30048-3 [pii]
LID - 10.1016/j.mad.2016.04.006 [doi]
AB  - Alpha-synuclein (syn) is the main component of proteinaceous inclusions known as 
      Lewy bodies (LBs), which are implicated in the pathogenesis of the 
      neurodegenerative diseases known as synucleinopathies, like Parkinson's disease 
      (PD). Aging is a major risk factor for PD and thus, interventions that delay 
      aging will have promising effects in PD and other synucleinopathies. Caloric 
      restriction (CR) is the only non-genetic intervention shown to promote lifespan 
      extension in several model organisms. CR has been shown to alleviate syn toxicity 
      and herein we confirmed the same effect on the yeast model for synucleinopathies 
      during chronological lifespan. The data gathered showed that TOR1 deletion also 
      results in similar longevity extension and abrogation of syn toxicity. 
      Intriguingly, these interventions were associated with decreased autophagy, which 
      was maintained at homeostatic levels. Autophagy maintenance at homeostatic levels 
      promoted by CR or TOR1 abrogation in syn-expressing cells was achieved by 
      decreasing Sir2 levels and activity. Furthermore, the opposite function of Tor1 
      and Sir2 in autophagy is probably associated with the maintenance of autophagy 
      activity at homeostatic levels, a central event linked to abrogation of syn 
      toxicity promoted by CR.
CI  - Copyright (c) 2016 Elsevier Ireland Ltd. All rights reserved.
FAU - Guedes, Ana
AU  - Guedes A
AD  - Life and Health Sciences Research Institute (ICVS), School of Health Sciences, 
      University of Minho, Braga, Portugal; ICVS/3B's - PT Government Associate 
      Laboratory, Braga, Guimaraes, Portugal.
FAU - Ludovico, Paula
AU  - Ludovico P
AD  - Life and Health Sciences Research Institute (ICVS), School of Health Sciences, 
      University of Minho, Braga, Portugal; ICVS/3B's - PT Government Associate 
      Laboratory, Braga, Guimaraes, Portugal. Electronic address: 
      pludovico@ecsaude.uminho.pt.
FAU - Sampaio-Marques, Belem
AU  - Sampaio-Marques B
AD  - Life and Health Sciences Research Institute (ICVS), School of Health Sciences, 
      University of Minho, Braga, Portugal; ICVS/3B's - PT Government Associate 
      Laboratory, Braga, Guimaraes, Portugal.
LA  - eng
PT  - Journal Article
DEP - 20160421
PL  - Ireland
TA  - Mech Ageing Dev
JT  - Mechanisms of ageing and development
JID - 0347227
RN  - 0 (SNCA protein, human)
RN  - 0 (Saccharomyces cerevisiae Proteins)
RN  - 0 (Silent Information Regulator Proteins, Saccharomyces cerevisiae)
RN  - 0 (alpha-Synuclein)
RN  - EC 2.7.1.137 (TOR1 protein, S cerevisiae)
RN  - EC 3.5.1.- (SIR2 protein, S cerevisiae)
RN  - EC 3.5.1.- (Sirtuin 2)
SB  - IM
MH  - *Autophagy
MH  - Phosphatidylinositol 3-Kinases/genetics/*metabolism
MH  - Saccharomyces cerevisiae/genetics/*metabolism
MH  - Saccharomyces cerevisiae Proteins/genetics/*metabolism
MH  - Silent Information Regulator Proteins, Saccharomyces 
      cerevisiae/genetics/*metabolism
MH  - Sirtuin 2/genetics/*metabolism
MH  - alpha-Synuclein/*biosynthesis/genetics
OTO - NOTNLM
OT  - Alpha-synuclein
OT  - Autophagy
OT  - Caloric restriction
OT  - Sirtuins
OT  - Synucleinopathies
EDAT- 2016/04/26 06:00
MHDA- 2017/08/11 06:00
CRDT- 2016/04/26 06:00
PHST- 2016/03/14 00:00 [received]
PHST- 2016/04/11 00:00 [revised]
PHST- 2016/04/18 00:00 [accepted]
PHST- 2016/04/26 06:00 [pubmed]
PHST- 2017/08/11 06:00 [medline]
PHST- 2016/04/26 06:00 [entrez]
AID - S0047-6374(16)30048-3 [pii]
AID - 10.1016/j.mad.2016.04.006 [doi]
PST - ppublish
SO  - Mech Ageing Dev. 2017 Jan;161(Pt B):270-276. doi: 10.1016/j.mad.2016.04.006. Epub 
      2016 Apr 21.