Mitochondrial import and enzymatic activity of PINK1 mutants associated to recessive parkinsonism.

@article{Silvestri2005MitochondrialIA,
  title={Mitochondrial import and enzymatic activity of PINK1 mutants associated to recessive parkinsonism.},
  author={Laura Silvestri and Viviana Caputo and Emanuele Bellacchio and Luigia Atorino and Bruno Dallapiccola and Enza Maria Valente and Giorgio Casari},
  journal={Human molecular genetics},
  year={2005},
  volume={14 22},
  pages={
          3477-92
        }
}
Parkinson's disease (PD) is a progressive neurodegenerative illness associated with a selective loss of dopaminergic neurons in the nigrostriatal pathway of the brain. Despite the overall rarity of the familial forms of PD, the identification of single genes linked to the disease has yielded crucial insights into possible mechanisms of neurodegeneration. Recently, a putative mitochondrial kinase, PINK1, has been found mutated in an inherited form of parkinsonism. Here, we describe that PINK1… 
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The current knowledge on PINK1 characteristics and functions are summarized, and the network of functional relationships that link Pink1 to other Parkinson’s disease-related proteins are analyzed.
Loss of PINK1 causes mitochondrial functional defects and increased sensitivity to oxidative stress
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It is demonstrated that mammalian Pink1 is important for mitochondrial function and provides critical protection against both intrinsic and environmental stress, suggesting a pathogenic mechanism by which loss of PINK1 may lead to nigrostriatal degeneration in PD.
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References

SHOWING 1-10 OF 51 REFERENCES
Hereditary Early-Onset Parkinson's Disease Caused by Mutations in PINK1
TLDR
The identification of two homozygous mutations affecting the PINK1 kinase domain in three consanguineous PARK6 families provide a direct molecular link between mitochondria and the pathogenesis of PD.
Early mitochondrial calcium defects in Huntington's disease are a direct effect of polyglutamines
TLDR
It is shown that lymphoblast mitochondria from patients with HD have a lower membrane potential and depolarize at lower calcium loads than do mitochondriaFrom controls, and mitochondrial calcium abnormalities occur early in HD pathogenesis and may be a direct effect of mutant huntingtin on the organelle.
Cloning of the Gene Containing Mutations that Cause PARK8-Linked Parkinson's Disease
Inducible expression of mutant alpha-synuclein decreases proteasome activity and increases sensitivity to mitochondria-dependent apoptosis.
Parkinson's disease (PD) is a common progressive neurodegenerative disorder caused by the loss of dopaminergic neurons in the substantia nigra. Although mutations in alpha-synuclein have been…
Parkinson's Disease Mechanisms and Models
Homozygous PINK1 C‐terminus mutation causing early‐onset parkinsonism
TLDR
It is confirmed that recessive mutations in PINK1 cause early‐onset parkinsonism and expand the associated clinical phenotype, which resembles closely parkin‐related disease.
Mutations in LRRK2 Cause Autosomal-Dominant Parkinsonism with Pleomorphic Pathology
Primary and secondary defects of the mitochondrial respiratory chain
  • A. Schapira
  • Biology
    Journal of Inherited Metabolic Disease
  • 2004
TLDR
Over 100 mutations of mitochondrial DNA (mtDNA) have been associated with human disease and it has become clear that the function of the respiratory chain may be impaired by mutations affecting other mitochondrial proteins or as a secondary phenomenon to other intracellular biochemical derangements.
alpha-synuclein promotes mitochondrial deficit and oxidative stress.
TLDR
Results suggest that abnormal accumulation of alpha-synuclein could lead to mitochondrial alterations that may result in oxidative stress and, eventually, cell death.
α-Synuclein Promotes Mitochondrial Deficit and Oxidative Stress
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