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Mitochondrial dysfunction in Parkinson's disease.

Keane PC, Kurzawa M, Blain PG, Morris CM - Parkinsons Dis (2011)

Bottom Line: A number of genes that have been shown to have links with inherited forms of PD encode mitochondrial proteins or proteins implicated in mitochondrial dysfunction, supporting the central involvement of mitochondria in PD.This involvement is corroborated by reports that environmental toxins that inhibit the mitochondrial respiratory chain have been shown to be associated with PD.This paper aims to illustrate the considerable body of evidence linking mitochondrial dysfunction with neuronal cell death in the substantia nigra pars compacta (SNpc) of PD patients and to highlight the important need for further research in this area.

View Article: PubMed Central - PubMed

Affiliation: Medical Toxicology Centre, Wolfson Unit, Newcastle University, Claremont Place, Newcastle upon Tyne NE2 4AA, UK.

ABSTRACT
Parkinson's disease (PD) is a progressive, neurodegenerative condition that has increasingly been linked with mitochondrial dysfunction and inhibition of the electron transport chain. This inhibition leads to the generation of reactive oxygen species and depletion of cellular energy levels, which can consequently cause cellular damage and death mediated by oxidative stress and excitotoxicity. A number of genes that have been shown to have links with inherited forms of PD encode mitochondrial proteins or proteins implicated in mitochondrial dysfunction, supporting the central involvement of mitochondria in PD. This involvement is corroborated by reports that environmental toxins that inhibit the mitochondrial respiratory chain have been shown to be associated with PD. This paper aims to illustrate the considerable body of evidence linking mitochondrial dysfunction with neuronal cell death in the substantia nigra pars compacta (SNpc) of PD patients and to highlight the important need for further research in this area.

No MeSH data available.


Related in: MedlinePlus

Structures of the PD-linked neurotoxins MPTP/MPP+, Rotenone, Paraquat, Diquat, and TaClo.
© Copyright Policy - open-access
Related In: Results  -  Collection


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fig3: Structures of the PD-linked neurotoxins MPTP/MPP+, Rotenone, Paraquat, Diquat, and TaClo.

Mentions: The first toxin that linked mitochondrial Complex I inhibition and PD was MPTP (Figure 3). MPTP is produced as a byproduct of the synthesis of a meperidine analogue with heroin-like properties [171]. Langston et al. described in 1983 that users of meperidine reported striking Parkinsonian symptoms and related this to the presence of MPTP [172]. It has also been shown to closely reproduce the DA degeneration and symptoms of PD in various animal experimental models [173, 174] and has been the most widely used toxin in animal models of PD [175]. MPTP readily crosses the blood brain barrier and is converted to the toxic 1-methyl-4-phenyl-2,3-dihydropyridium ion (MPP+) (Figure 3) by monoamine oxidase B in astrocytes [176] and is then taken up into DA neurons by DAT seen as a reduction in MPTP toxicity in DAT deficient mice [177]. MPP+ is taken up into mitochondria via passive transport due to the large mitochondrial transmembrane gradient [178], where MPP+ inhibits mitochondrial Complex I [179]. This inhibition of Complex I leads to cell death via energy deficits [180], free radical and ROS generation [181], and possibly excitotoxicity [182]. In an MPTP mouse model of PD, α-synuclein is nitrated [183], providing another link between MPTP and PD. However, despite all of the evidence of links between MPTP and PD, there are differences between MPTP models of PD and idiopathic PD with variations in disease progression, an acute onset, and the lack of typical LB formation [184].


Mitochondrial dysfunction in Parkinson's disease.

Keane PC, Kurzawa M, Blain PG, Morris CM - Parkinsons Dis (2011)

Structures of the PD-linked neurotoxins MPTP/MPP+, Rotenone, Paraquat, Diquat, and TaClo.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3065167&req=5

fig3: Structures of the PD-linked neurotoxins MPTP/MPP+, Rotenone, Paraquat, Diquat, and TaClo.
Mentions: The first toxin that linked mitochondrial Complex I inhibition and PD was MPTP (Figure 3). MPTP is produced as a byproduct of the synthesis of a meperidine analogue with heroin-like properties [171]. Langston et al. described in 1983 that users of meperidine reported striking Parkinsonian symptoms and related this to the presence of MPTP [172]. It has also been shown to closely reproduce the DA degeneration and symptoms of PD in various animal experimental models [173, 174] and has been the most widely used toxin in animal models of PD [175]. MPTP readily crosses the blood brain barrier and is converted to the toxic 1-methyl-4-phenyl-2,3-dihydropyridium ion (MPP+) (Figure 3) by monoamine oxidase B in astrocytes [176] and is then taken up into DA neurons by DAT seen as a reduction in MPTP toxicity in DAT deficient mice [177]. MPP+ is taken up into mitochondria via passive transport due to the large mitochondrial transmembrane gradient [178], where MPP+ inhibits mitochondrial Complex I [179]. This inhibition of Complex I leads to cell death via energy deficits [180], free radical and ROS generation [181], and possibly excitotoxicity [182]. In an MPTP mouse model of PD, α-synuclein is nitrated [183], providing another link between MPTP and PD. However, despite all of the evidence of links between MPTP and PD, there are differences between MPTP models of PD and idiopathic PD with variations in disease progression, an acute onset, and the lack of typical LB formation [184].

Bottom Line: A number of genes that have been shown to have links with inherited forms of PD encode mitochondrial proteins or proteins implicated in mitochondrial dysfunction, supporting the central involvement of mitochondria in PD.This involvement is corroborated by reports that environmental toxins that inhibit the mitochondrial respiratory chain have been shown to be associated with PD.This paper aims to illustrate the considerable body of evidence linking mitochondrial dysfunction with neuronal cell death in the substantia nigra pars compacta (SNpc) of PD patients and to highlight the important need for further research in this area.

View Article: PubMed Central - PubMed

Affiliation: Medical Toxicology Centre, Wolfson Unit, Newcastle University, Claremont Place, Newcastle upon Tyne NE2 4AA, UK.

ABSTRACT
Parkinson's disease (PD) is a progressive, neurodegenerative condition that has increasingly been linked with mitochondrial dysfunction and inhibition of the electron transport chain. This inhibition leads to the generation of reactive oxygen species and depletion of cellular energy levels, which can consequently cause cellular damage and death mediated by oxidative stress and excitotoxicity. A number of genes that have been shown to have links with inherited forms of PD encode mitochondrial proteins or proteins implicated in mitochondrial dysfunction, supporting the central involvement of mitochondria in PD. This involvement is corroborated by reports that environmental toxins that inhibit the mitochondrial respiratory chain have been shown to be associated with PD. This paper aims to illustrate the considerable body of evidence linking mitochondrial dysfunction with neuronal cell death in the substantia nigra pars compacta (SNpc) of PD patients and to highlight the important need for further research in this area.

No MeSH data available.


Related in: MedlinePlus