PMID- 29793507
OWN - NLM
STAT- MEDLINE
DCOM- 20181109
LR  - 20240314
IS  - 1750-1326 (Electronic)
IS  - 1750-1326 (Linking)
VI  - 13
IP  - 1
DP  - 2018 May 24
TI  - Targeting energy metabolism via the mitochondrial pyruvate carrier as a novel 
      approach to attenuate neurodegeneration.
PG  - 28
LID - 10.1186/s13024-018-0260-x [doi]
LID - 28
AB  - Several molecular pathways are currently being targeted in attempts to develop 
      disease-modifying therapies to slow down neurodegeneration in Parkinson's 
      disease. Failure of cellular energy metabolism has long been implicated in 
      sporadic Parkinson's disease and recent research on rare inherited forms of 
      Parkinson's disease have added further weight to the importance of energy 
      metabolism in the disease pathogenesis. There exists a new class of anti-diabetic 
      insulin sensitizers in development that inhibit the mitochondrial pyruvate 
      carrier (MPC), a protein which mediates the import of pyruvate across the inner 
      membrane of mitochondria. Pharmacological inhibition of the MPC was recently 
      found to be strongly neuroprotective in multiple neurotoxin-based and genetic 
      models of neurodegeneration which are relevant to Parkinson's disease. In this 
      review, we summarize the neuroprotective effects of MPC inhibition and discuss 
      the potential putative underlying mechanisms. These mechanisms involve 
      augmentation of autophagy via attenuation of the activity of the mammalian target 
      of rapamycin (mTOR) in neurons, as well as the inhibition of neuroinflammation, 
      which is at least partly mediated by direct inhibition of MPC in glia cells. We 
      conclude that MPC is a novel and potentially powerful therapeutic target that 
      warrants further study in attempts to slow Parkinson's disease progression.
FAU - Quansah, Emmanuel
AU  - Quansah E
AD  - Center for Neurodegenerative Science, Van Andel Research Institute, Grand Rapids, 
      333 Bostwick Ave, Michigan, 49503, USA.
FAU - Peelaerts, Wouter
AU  - Peelaerts W
AD  - Center for Neurodegenerative Science, Van Andel Research Institute, Grand Rapids, 
      333 Bostwick Ave, Michigan, 49503, USA.
AD  - KU Leuven, Laboratory for Gene Therapy and Neurobiology, 3000, Leuven, Belgium.
FAU - Langston, J William
AU  - Langston JW
AD  - Stanford Udall Center, Department of Pathology, Stanford University, Palo Alto, 
      CA, USA.
FAU - Simon, David K
AU  - Simon DK
AD  - Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, 
      Boston, MA, USA.
FAU - Colca, Jerry
AU  - Colca J
AD  - Metabolic Solutions Development Company, Kalamazoo, MI, 49007, USA.
FAU - Brundin, Patrik
AU  - Brundin P
AD  - Center for Neurodegenerative Science, Van Andel Research Institute, Grand Rapids, 
      333 Bostwick Ave, Michigan, 49503, USA. patrik.brundin@vai.org.
LA  - eng
GR  - P50 NS062684/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20180524
PL  - England
TA  - Mol Neurodegener
JT  - Molecular neurodegeneration
JID - 101266600
RN  - 0 (MPC1 protein, human)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (Mitochondrial Membrane Transport Proteins)
RN  - 0 (Monocarboxylic Acid Transporters)
SB  - IM
MH  - Animals
MH  - Energy Metabolism/*physiology
MH  - Humans
MH  - Membrane Transport Proteins/*metabolism
MH  - Mitochondrial Membrane Transport Proteins
MH  - Monocarboxylic Acid Transporters
MH  - Nerve Degeneration/*metabolism
MH  - Parkinson Disease/*metabolism
PMC - PMC5968614
OTO - NOTNLM
OT  - Insulin sensitizers
OT  - Mitochondrial pyruvate carrier
OT  - Neurodegeneration
OT  - Parkinson's disease
COIS- COMPETING INTERESTS: PB has received commercial support as a consultant from 
      Renovo Neural, Inc., Cellular Dynamics International, Axial Biotherapeutics, 
      Roche, Teva Inc., Lundbeck A/S, NeuroDerm, AbbVie, ClearView Healthcare, FCB 
      Health, IOS Press Partners and Capital Technologies, Inc. PB has ownership 
      interests in Acousort AB. EQ and PB are conducting sponsored research on behalf 
      of Roche and Lundbeck A/S. JC is co-founder and part-owner of MSDC. PUBLISHER'S 
      NOTE: Springer Nature remains neutral with regard to jurisdictional claims in 
      published maps and institutional affiliations.
EDAT- 2018/05/26 06:00
MHDA- 2018/11/10 06:00
PMCR- 2018/05/24
CRDT- 2018/05/26 06:00
PHST- 2018/03/21 00:00 [received]
PHST- 2018/05/17 00:00 [accepted]
PHST- 2018/05/26 06:00 [entrez]
PHST- 2018/05/26 06:00 [pubmed]
PHST- 2018/11/10 06:00 [medline]
PHST- 2018/05/24 00:00 [pmc-release]
AID - 10.1186/s13024-018-0260-x [pii]
AID - 260 [pii]
AID - 10.1186/s13024-018-0260-x [doi]
PST - epublish
SO  - Mol Neurodegener. 2018 May 24;13(1):28. doi: 10.1186/s13024-018-0260-x.