PMID- 19651206
OWN - NLM
STAT- MEDLINE
DCOM- 20100616
LR  - 20211020
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1802
IP  - 1
DP  - 2010 Jan
TI  - The mitochondrial permeability transition pore: a molecular target for 
      amyotrophic lateral sclerosis therapy.
PG  - 186-97
LID - 10.1016/j.bbadis.2009.07.009 [doi]
AB  - Effective therapies are needed for the treatment of amyotrophic lateral sclerosis 
      (ALS), a fatal type of motor neuron disease. Morphological, biochemical, 
      molecular genetic, and cell/animal model studies suggest that mitochondria have 
      potentially diverse roles in neurodegenerative disease mechanisms and neuronal 
      cell death. In human ALS, abnormalities have been found in mitochondrial 
      structure, mitochondrial respiratory chain enzymes, and mitochondrial cell death 
      proteins indicative of some non-classical form of programmed cell death. Mouse 
      models of ALS are beginning to reveal possible principles governing the biology 
      of selective neuronal vulnerability that implicate mitochondria. This minireview 
      summarizes work on the how malfunctioning mitochondria might contribute to 
      neuronal death in ALS through the biophysical entity called the mitochondrial 
      permeability pore (mPTP). The major protein components of the mPTP are enriched 
      in mouse motor neurons. Early in the course of disease in ALS mice expressing 
      human mutant superoxide dismutase-1, mitochondria in motor neurons undergo 
      trafficking abnormalities and dramatic remodeling resulting in the formation of 
      mega-mitochondria and coinciding with increased protein carbonyl formation and 
      nitration of mPTP components. The genetic deletion of a major mPTP component, 
      cyclophilin D, has robust effects in ALS mice by delaying disease onset and 
      extending survival. Thus, attention should be directed to the mPTP as a rational 
      target for the development of drugs designed to treat ALS.
FAU - Martin, Lee J
AU  - Martin LJ
AD  - Department of Pathology, Division of Neuropathology, Johns Hopkins University 
      School of Medicine, Baltimore, Maryland 21205-2196, USA. martinl@jhmi.edu
LA  - eng
GR  - R01 NS052098/NS/NINDS NIH HHS/United States
GR  - NS052098/NS/NINDS NIH HHS/United States
GR  - R01 AG016282-09/AG/NIA NIH HHS/United States
GR  - AG016282/AG/NIA NIH HHS/United States
GR  - R01 NS065895/NS/NINDS NIH HHS/United States
GR  - R01 AG016282/AG/NIA NIH HHS/United States
GR  - NS065895/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Review
DEP - 20090803
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 0 (Mitochondrial Membrane Transport Proteins)
RN  - 0 (Mitochondrial Permeability Transition Pore)
SB  - IM
MH  - Amyotrophic Lateral Sclerosis/drug therapy/*metabolism
MH  - Animals
MH  - Cell Death
MH  - Humans
MH  - Mice
MH  - Mitochondria/metabolism
MH  - Mitochondrial Membrane Transport Proteins/*metabolism
MH  - Mitochondrial Permeability Transition Pore
MH  - Models, Biological
PMC - PMC2790555
MID - NIHMS144232
EDAT- 2009/08/05 09:00
MHDA- 2010/06/17 06:00
PMCR- 2011/01/01
CRDT- 2009/08/05 09:00
PHST- 2009/06/26 00:00 [received]
PHST- 2009/07/22 00:00 [revised]
PHST- 2009/07/23 00:00 [accepted]
PHST- 2009/08/05 09:00 [entrez]
PHST- 2009/08/05 09:00 [pubmed]
PHST- 2010/06/17 06:00 [medline]
PHST- 2011/01/01 00:00 [pmc-release]
AID - S0925-4439(09)00162-8 [pii]
AID - 10.1016/j.bbadis.2009.07.009 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 2010 Jan;1802(1):186-97. doi: 10.1016/j.bbadis.2009.07.009. 
      Epub 2009 Aug 3.