)| PMID |
16050975 ( ) |
|---|---|
| Title | Mitochondrial dysfunction and its role in motor neuron degeneration in ALS. |
| Abstract | Mitochondria play a pivotal role in many metabolic and apoptotic pathways that regulate the life and death of cells. Accumulating evidence suggests that mitochondrial dysfunction is involved in the pathogenesis of amyotrophic lateral sclerosis (ALS). Mitochondrial dysfunction may cause motor neuron death by predisposing them to calcium-mediated excitotoxicity, by increasing generation of reactive oxygen species, and by initiating the intrinsic apoptotic pathway. Morphological and biochemical mitochondrial abnormalities have been described in sporadic human ALS cases, but the implications of these findings in terminally ill individuals or in post-mortem tissues are difficult to decipher. However, remarkable mitochondrial abnormalities have also been identified in transgenic mouse models of familial ALS expressing mutant Cu, Zn superoxide dismutase (SOD1). Detailed studies in these mouse models indicate that mitochondrial abnormalities begin prior to the clinical and pathological onset of the disease, suggesting that mitochondrial dysfunction may be causally involved in the pathogenesis of ALS. Although the mechanisms whereby mutant SOD1 damages mitochondria remain to be fully understood, the finding that a portion of mutant SOD1 is localized in mitochondria, where it forms aberrant aggregates and protein interactions, has opened a number of avenues of investigation. The future challenges are to devise models to better understand the effects of mutant SOD1 in mitochondria and the relative contribution of mitochondrial dysfunction to the pathogenesis of ALS, as well as to identify therapeutic approaches that target mitochondrial dysfunction and its consequences. University, 525 East 68th Street A-501, New York, NY 10021, USA. |
NOTE: Color highlight is limited to the abstract and SciMiner text-mining mode. If you see much more identified targets below from "Targets by SciMiner Summary" and "Targets by SciMiner Full list", they may have been identified from the full text.
Targets by SciMiner Summary
| HUGO ID | Symbol | Target Name | #Occur | ActualStr |
|---|---|---|---|---|
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | 91 | superoxide dismutase 1 | SOD1 | SOD1-related | hSOD1 | SOD1-induced | |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | 6 | Bcl-2 | bcl 2 | |
| 19986 | CYCS | cytochrome c, somatic | 4 | cytochrome c | |
| 1613 | CCS | copper chaperone for superoxide dismutase | 2 | CCS | |
| 8768 | AIFM1 | apoptosis-inducing factor, mitochondrion-associated, 1 | 2 | apoptosis inducing factor | AIF | |
| 1499 | CASP1 | caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase) | 1 | caspase 1 | |
| 10417 | RPS27A | ribosomal protein S27a | 1 | ubiquitin | |
| 4572 | GRIA2 | glutamate receptor, ionotropic, AMPA 2 | 1 | gluR2 | |
| 1511 | CASP9 | caspase 9, apoptosis-related cysteine peptidase | 1 | caspase 9 | |
| 3346 | ENDOG | endonuclease G | 1 | endoG | |
| 7711 | NDUFS4 | NADH dehydrogenase (ubiquinone) Fe-S protein 4, 18kDa (NADH-coenzyme Q reductase) | 1 | mitochondrial respiratory chain complex i | |
Targets by SciMiner Full list
| HUGO ID | Symbol | Name | ActualStr | Score | FlankingText |
|---|---|---|---|---|---|
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | of familial ALS expressing mutant Cu Zn superoxide dismutase (SOD1) SOD1 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | Although the mechanisms whereby mutant SOD1 damages mitochondria remain to be fully understood the finding that |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | be fully understood the finding that a portion of mutant SOD1 is localized in mitochondria where it forms aberrant aggregates and |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | to devise models to better understand the effects of mutant SOD1 in mitochondria and the relative contribution of mitochondrial dysfunction to |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | Familial ALS due to SOD1 mutations and transgenic mouse models |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | to mutations in the gene encoding superoxide dismutase 1 (SOD1; SOD1 Cu Zn dismutase MIM147450 ( Rosen et al. 1993 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | SOD1 is a ubiquitous metalloprotein that prevents damage by oxygen-mediated free |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | The symptoms and pathology of FALS patients with SOD1 mutations closely resemble those of patients with SALS and the |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | and pathologic alterations in motor neurons from mice expressing mutant SOD1 are also strikingly similar to those found in SALS patients |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | Since the initial report of SOD1 mutations ( Rosen et al. 1993 more than 100 different |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | al. 1993 more than 100 different mutated forms of the SOD1 gene most of which are missense mutations have been identified |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | Because several pathogenic mutations do not affect SOD1 activity significantly ( Borchelt et al. 1994 a toxic _amp_#x2018 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | confirmed by several transgenic studies in which mice expressing mutant SOD1 develop motor neuron degeneration despite an overall increase in their |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | develop motor neuron degeneration despite an overall increase in their SOD1 activity ( Xu 2000 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | Mutant SOD1 is expressed ubiquitously but the pathological process leading to the |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | The tissue selectivity of SOD1 toxicity is a puzzling problem that has yet to be |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | While mouse models that express mutant SOD1 ubiquitously (similar similar to what happens in humans develop motor |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | develop motor neuron degeneration and ALS models that express mutant SOD1 exclusively either in the motor neurons or in astrocytes do |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | this view in chimeric mice that contain a mixture of SOD1 mutant and wild type cells motor neurons with wild type |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | mutant and wild type cells motor neurons with wild type SOD1 develop signs of degeneration whereas non-neuronal cells with wild type |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | to attenuate the degeneration of motor neurons with the mutant SOD1 gene ( Clement et al. 2003 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | However thanks to the availability of the mutant SOD1 transgenic mice that have provided an excellent platform to investigate |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | neuron degeneration in models of FALS caused by mutations in SOD1 gene |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | Mitochondrial involvement in models of ALS created by introduction of SOD1 mutants |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | A striking pathological feature observed in transgenic mice expressing SOD1 mutants G93A or G37R is the presence of membrane bound |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | evidence obtained in cellular models indicate that expression of mutant SOD1 is not only associated with mitochondrial morphological changes but also |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | observed in neuroblastoma cells transfected with the mutated form of SOD1 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | found in cultured motor neuron-like cells expressing mutated forms of SOD1 ( Menzies et al. 2002 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | reported that mitochondrial bioenergetics is impaired in the G93A mutant SOD1 mouse model of FALS |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | Recently we have found that the bioenergetic failure in the SOD1 mutant mice causes an impairment of mitochondrial calcium loading capacity |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | Impaired mitochondrial calcium loading capacity in SOD1 mutant mice may produce two consequences |
| 4572 | GRIA2 | glutamate receptor, ionotropic, AMPA 2 | gluR2 | 1.3 | supported by the observation that overexpression of the calcium impermeable gluR2 subunit in motor neurons improves life span and motor functions |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 1.7 | Consistent with this view antioxidant agents extended survival of mutant hSOD1 transgenic mice ( Jung et al. 2001 and Wu et |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | The expression of mutant SOD1 predisposes cultured neuronal cells to activation of apoptosis in response |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | 3 are activated sequentially in differentiated neuroblastoma cells expressing mutant SOD1 in response to oxidative stress ( Pasinelli et al. 1998 |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | Bcl-2 | 1.8 | al. 2000 and the overexpression of the mitochondrial anti-apoptotic protein Bcl-2 ( Kostic et al. 1997 slow motor neuron degeneration and |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | 1997 slow motor neuron degeneration and extend the survival of SOD1 mutant mice |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | For example mutant SOD1 mice genetically lacking caspase 11 an upstream regulator of the |
| 8768 | AIFM1 | apoptosis-inducing factor, mitochondrion-associated, 1 | AIF | 0.6 | pro-apoptotic factors such as cytochrome c apoptosis inducing factor (AIF), AIF and endoG from individual mitochondria perhaps in response to local |
| 3346 | ENDOG | endonuclease G | endoG | 0.1 | such as cytochrome c apoptosis inducing factor (AIF), AIF and endoG from individual mitochondria perhaps in response to local calcium mediated |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | Mechanisms of mitochondrial dysfunction in SOD1 FALS mitochondrial localization of SOD1 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | Mechanisms of mitochondrial dysfunction in SOD1 FALS mitochondrial localization of SOD1 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | changes and the biochemical abnormalities observed in mice expressing mutant SOD1 are still the object of intense investigation |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | Two fundamental questions remain to be answered how is mutant SOD1 causing mitochondrial degeneration and dysfunction and is mitochondrial dysfunction necessary |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1-induced | 1.7 | necessary and/or and or sufficient for the development of mutant SOD1-induced motor neuron degeneration |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | answering these questions is the finding that a portion of SOD1 (most most of which is cytosolic is actually localized in |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | SOD1 enzymatic activity in rat liver mitochondria was first detected by |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | Recently the existence of SOD1 in mitochondria of eukaryotic cells has been confirmed by several |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | By cell fractionation and mitochondrial purification techniques SOD1 was detected in the mitochondria of the yeast S cerevisiae |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | 2001 and Higgins et al. 2002 have independently demonstrated that SOD1 localizes in the mitochondria of motor neurons in the spinal |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | These investigators showed that both wild type and mutant SOD1 are localized in mitochondria |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | addition Field and colleagues have showed that the retention of SOD1 inside yeast mitochondria is dependent upon the interaction with its |
| 1613 | CCS | copper chaperone for superoxide dismutase | CCS | 0.9 | mitochondria is dependent upon the interaction with its copper chaperone CCS since SOD1 mutants that are unable to interact with CCS |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | dependent upon the interaction with its copper chaperone CCS since SOD1 mutants that are unable to interact with CCS _amp_#x2018 leak |
| 1613 | CCS | copper chaperone for superoxide dismutase | CCS | 0.9 | CCS since SOD1 mutants that are unable to interact with CCS _amp_#x2018 leak out_amp_#x2019 of mitochondria ( Field et al. 2003 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | Based on mitochondrial fractionation experiments several groups have proposed that SOD1 concentrates mostly in the intermembrane space of mitochondria ( Okado-Matsumoto |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | Recent experiments suggest that in mice expressing transgenic human SOD1 a portion of mutant SOD1 may also localize in the |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | in mice expressing transgenic human SOD1 a portion of mutant SOD1 may also localize in the matrix space of mitochondria where |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | matrix space of mitochondria where it forms large aggregates containing SOD1 and possibly other mitochondrial matrix proteins ( Vijayvergiya and Manfredi |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | Although how mutant SOD1 damages mitochondria has not been unequivocally defined several non-mutually exclusive |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | Higgins and colleagues have observed that SOD1 and cytochrome c a resident protein of the intermembrane space |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | colocalize at the early stages of mitochondrial vacuolization in mutant SOD1 transgenic mice |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | They also observed large aggregates of SOD1 immunoreactive material within the vacuoles |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | and colleagues have recently reported that in transgenic mice mutant SOD1 but not wild type SOD1 associates preferentially with mitochondria of |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | that in transgenic mice mutant SOD1 but not wild type SOD1 associates preferentially with mitochondria of the spinal cord |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | They proposed that mutant SOD1 progressively accumulates and aggregates on the outer membrane causing _amp_#x2018 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | of FALS it would suggest that mitochondrial localization of mutant SOD1 resulting in protein import impairment is an important contributor to |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | mentioned above where both wild type and mutant transgenic human SOD1 were detected in the mitochondria of various tissues including brain |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | Discrepancies in terms of the localization of the wild type SOD1 in these studies may be attributed to the differences in |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | to the differences in the strategies for mitochondrial purification and SOD1 detection and will require further experiments to be reconciled |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | to clarify the specificity and the exact intramitochondrial localization of SOD1 there is general agreement that mutant SOD1 tends to form |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | intramitochondrial localization of SOD1 there is general agreement that mutant SOD1 tends to form aggregates in mitochondria with potential pathogenic effects |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | In particular it will be interesting to assess whether mutant SOD1 forms abnormal interactions with other mitochondrial proteins which may lead |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | such potentially harmful protein-protein interactions is the binding of mutant SOD1 with Bcl-2 ( Pasinelli et al. 2004 |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | Bcl-2 | 1.8 | harmful protein-protein interactions is the binding of mutant SOD1 with Bcl-2 ( Pasinelli et al. 2004 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | in protein import and energy metabolism may interact with mutant SOD1 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | Because SOD1 is present both in the cytosol and in mitochondria it |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | mitochondrial dysfunction to a direct toxic effect of mitochondrial mutant SOD1 alone |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | mitochondrial dysfunction may arise as a consequence of cytosolic mutant SOD1 toxicity cannot be ruled out |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | For example mutant cytosolic SOD1 could promote aberrant production of reactive oxygen species ( Estevez |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | are prominent pathological features in the G93A and the G37R SOD1 transgenic mice other mouse models such as those transgenic for |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | It remains to be tested whether some SOD1 mutants can affect mitochondrial functions without causing overt morphological changes |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | Since most of the work on the bioenergetics of SOD1 mutant mitochondria has been done in the G93A model in |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | function and protecting mitochondria from the pro-apoptotic effect of mutant SOD1 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | of the mitochondrial apoptotic pathway extend the lifespan of mutant SOD1 transgenic mice |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | could be to generate cellular and animal models where mutant SOD1 is selectively localized in the mitochondria |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | Mitochondrial targeting of SOD1 could be achieved by appending specific mitochondrial targeting signals on |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | Conversely the identification of protein domains in SOD1 crucial for its mitochondrial import could allow for the generation |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | the generation of models where the mitochondrial content of mutant SOD1 is drastically reduced or eliminated |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | The comparison of these models with the ones where mutant SOD1 is expressed in both the cytosolic and mitochondrial compartments will |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | compartments will help us defining the role that mitochondrial mutant SOD1 plays in mitochondrial dysfunction and ultimately in the pathogenesis of |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1-related | 1.7 | Fig 1._amp_#xa0 Diagram of potential pathways of mitochondrial involvement in SOD1-related ALS |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | Mutant SOD1 has been proposed to affect mitochondrial functions in several ways |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | Mutant SOD1 may affect mitochondria directly within the organelles or indirectly from |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.5 | Within mitochondria mutant SOD1 may interfere with the anti-apoptotic function of Bcl-2 ( Pasinelli |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | Bcl-2 | 1.8 | mitochondria mutant SOD1 may interfere with the anti-apoptotic function of Bcl-2 ( Pasinelli et al. 2004 affect mitochondrial import by interfering |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | superoxide dismutase | 1.0 | however remarkable mitochondrial abnormalities have also been identified in transgenic mouse models of familial als expressing mutant cu zn superoxide dismutase sod1 . |
| 10417 | RPS27A | ribosomal protein S27a | ubiquitin | 1.0 | ons are bunina bodies round eosinophilic inclusions containing a homogeneous granular matrix surrounded by vesicular and tubular structures tomonaga et al. 1978 and skein like inclusions that contain ubiquitin and are comprised of bundles of 15_amp_#x2013;20 nm thick neurofilaments migheli et al. 1990 and sasaki and maruyama 1992 . |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | superoxide dismutase 1 | 1.0 | approximately 20% of fals cases are due to mutations in the gene encoding superoxide dismutase 1 sod1; cu zn dismutase; mim147450 rosen et al. 1993 . |
| 7711 | NDUFS4 | NADH dehydrogenase (ubiquinone) Fe-S protein 4, 18kDa (NADH-coenzyme Q reductase) | mitochondrial respiratory chain complex i | 1.0 | deficits in the activities of mitochondrial respiratory chain complex i wiedemann et al. 1998 and complex iv vielhaber et al. 2000 have been identified in the skeletal muscle and in the spinal cord of sals patients borthwick et al. 1999 and wiedemann et al. 2002 . |
| 1499 | CASP1 | caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase) | caspase 1 | 1.0 | for example caspase 1 and 3 are activated sequentially in differentiated neuroblastoma cells expressing mutant sod1 in response to oxidative stress pasinelli et al. 1998 and pasinelli et al. 2000 . |
| 1511 | CASP9 | caspase 9, apoptosis-related cysteine peptidase | caspase 9 | 1.0 | in spinal motor neurons of g93a transgenic mice cytochrome c is released from mitochondria leading to caspase 9 activation guegan et al. 2001 . |
| 19986 | CYCS | cytochrome c, somatic | cytochrome c | 1.0 | in spinal motor neurons of g93a transgenic mice cytochrome c is released from mitochondria leading to caspase 9 activation guegan et al. 2001 . |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | bcl 2 | 1.0 | both inhibition of caspase activation li et al. 2000 and the overexpression of the mitochondrial anti apoptotic protein bcl 2 kostic et al. 1997 slow motor neuron degeneration and extend the survival of sod1 mutant mice. |
| 8768 | AIFM1 | apoptosis-inducing factor, mitochondrion-associated, 1 | apoptosis inducing factor | 1.0 | one may envision a scenario where mitochondrial dysfunction results in quantal releases of pro apoptotic factors such as cytochrome c apoptosis inducing factor aif and endog from individual mitochondria perhaps in response to local calcium mediated toxicity for example under excitatory synapses. |
| 19986 | CYCS | cytochrome c, somatic | cytochrome c | 1.0 | one may envision a scenario where mitochondrial dysfunction results in quantal releases of pro apoptotic factors such as cytochrome c apoptosis inducing factor aif and endog from individual mitochondria perhaps in response to local calcium mediated toxicity for example under excitatory synapses. |
| 19986 | CYCS | cytochrome c, somatic | cytochrome c | 1.0 | higgins and colleagues have observed that sod1 and cytochrome c a resident protein of the intermembrane space colocalize at the early stages of mitochondrial vacuolization in mutant sod1 transgenic mice. |
| 19986 | CYCS | cytochrome c, somatic | cytochrome c | 1.0 | the expanded outer membrane could become porous and allow for leakage of cytochrome c and other pro apoptotic molecules into the cytosol potentially triggering the apoptotic cascade higgins et al. 2003 and xu et al. 2004 . |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | bcl 2 | 1.0 | an example of such potentially harmful protein protein interactions is the binding of mutant sod1 with bcl 2 pasinelli et al. 2004 . |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | bcl 2 | 1.0 | within mitochondria mutant sod1 may interfere with the anti apoptotic function of bcl 2 pasinelli et al. 2004 affect mitochondrial import by interfering with the translocation machinery tom/tim liu et al. 2004 generate toxic free radicals ros via aberrant superoxide chemistry estevez et |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | superoxide dismutase 1 | 1.0 | superoxide dismutase 1|superoxide dismutase| |