Parkinson disease: etiology, pathogenesis and future of gene therapy

Shastry, Barkur S.

doi:10.1016/s0168-0102(01)00254-1

Cited by 98 publications

(72 citation statements)

References 67 publications

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“…Although a genetic predisposition has been identified in a subset of patients with PD and several other risk factors for PD have been identified, 1-3 the cause and etiology of PD are largely unknown. [1][2][3][4][5] In addition to multiple other effects, the impaired basal ganglia function in PD leads to alterations in gait and balance. These motor changes in PD often restrict functional independence and are a major cause of morbidity and mortality among these patients.…”

Section: Introductionmentioning

confidence: 99%

Gait dynamics in Parkinson’s disease: Common and distinct behavior among stride length, gait variability, and fractal-like scaling

Hausdorff

2009

Chaos: An Interdisciplinary Journal of Nonlinear Science

483

394

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Parkinson’s disease (PD) is a common, debilitating neurodegenerative disease. Gait disturbances are a frequent cause of disability and impairment for patients with PD. This article provides a brief introduction to PD and describes the gait changes typically seen in patients with this disease. A major focus of this report is an update on the study of the fractal properties of gait in PD, the relationship between this feature of gait and stride length and gait variability, and the effects of different experimental conditions on these three gait properties. Implications of these findings are also briefly described. This update highlights the idea that while stride length, gait variability, and fractal scaling of gait are all impaired in PD, distinct mechanisms likely contribute to and are responsible for the regulation of these disparate gait properties.

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Section: Introductionmentioning

confidence: 99%

Gait dynamics in Parkinson’s disease: Common and distinct behavior among stride length, gait variability, and fractal-like scaling

Hausdorff

2009

Chaos: An Interdisciplinary Journal of Nonlinear Science

483

394

View full text Add to dashboard Cite

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“…Available therapies aim at replacing dopamine in the brain to restore motor function. 5,6 However, it is essential to develop novel therapeutic interventions that block or slow down the ongoing degenerative process. A neuroprotective strategy, interfering with neuronal cell death or preventing neuronal dysfunction, may become the center of interest.…”

Section: Introductionmentioning

confidence: 99%

Prevention of onset of Parkinson’s disease by in vivo gene transfer of human hepatocyte growth factor in rodent model: a model of gene therapy for Parkinson’s disease

et al. 2006

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Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra (SNi). As neurotrophic factors support the survival and enhance the function of dopaminergic neurons, gene therapy using neurotrophic factors has become the center of interest. Thus, we focused on hepatocyte growth factor (HGF) as a neurotrophic and angiogenic growth factor. At 7 days before injection of 6-hydroxydopamine into the SNi, stereotaxic transfection of human HGF or lacZ plasmid was performed into the unilateral striatum of rats. Expression of human HGF in the injected sites could be detected in rats transfected with HGF plasmid DNA, using immunohistochemical staining. Consistently, human immunoreactive HGF protein could be detected at least up to 12 days after transfection. Interestingly, PD rats transfected with lacZ demonstrated amphetamine-induced rotational asymmetry. However, transfection of HGF plasmid DNA resulted in significant inhibition of abnormal rotation up to 24 weeks in a dose-dependent manner. Over 90% of dopaminergic neurons were lost in PD rats transfected with lacZ, whereas over 70% survived in rats transfected with HGF, as assessed by immunohistochemical staining. Overall, the present study demonstrated that overexpression of HGF prevented neuronal death in a PD rat model, providing a potential novel therapy for PD.

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“…The intracellular cascade of events leading to neuronal death is still poorly understood, and appears to involve multiple death programs and inflammatory responses potentially related to microglial activation. 1 Therapeutic strategies to inhibit apoptosis were considered, but they met with relatively limited success, 2,3 and the surviving neurons did not retain normal synaptic function. 4 Further confounding decisions about the appropriate choice of therapy, recent findings suggest that the death of dopaminergic neurons is not due to canonical apoptosis, but rather to caspase-independent programmed cell death (PCD) [5][6][7][8] or necrosis.…”

Section: Introductionmentioning

confidence: 99%

ICP10PK inhibits calpain-dependent release of apoptosis-inducing factor and programmed cell death in response to the toxin MPP+

et al. 2008

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Apoptosis is a widely accepted component of the pathogenesis of Parkinson's disease (PD), a debilitating neurodegenerative disorder characterized by loss of dopaminergic neurons in the substantia nigra. However, additional death programs were implicated, and current understanding of the cycle of intracellular events that leads to the demise of these neurons is limited. Gene therapy strategies were proposed to inhibit apoptosis, but they have met with relatively limited success. Here we report that the antiapoptotic herpes simplex virus type 2 gene ICP10PK protects neuronally differentiated PC12 cells from death caused by 1-methyl-4-phenylpyridinium (in vitro PD model) through inhibition of calpain I activation and the resulting inhibition of Bax translocation to the mitochondria, apoptosis-inducing factor release and caspase-3 activation. Neuroprotection is through ICP10PK-mediated activation of the PI3-K/Akt survival pathway and upregulation/stabilization of the antiapoptotic protein Bcl-2 and the cytoprotective chaperone heat-shock protein 70.

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Parkinson disease: etiology, pathogenesis and future of gene therapy

Cited by 98 publications

References 67 publications

Gait dynamics in Parkinson’s disease: Common and distinct behavior among stride length, gait variability, and fractal-like scaling

Gait dynamics in Parkinson’s disease: Common and distinct behavior among stride length, gait variability, and fractal-like scaling

Prevention of onset of Parkinson’s disease by in vivo gene transfer of human hepatocyte growth factor in rodent model: a model of gene therapy for Parkinson’s disease

ICP10PK inhibits calpain-dependent release of apoptosis-inducing factor and programmed cell death in response to the toxin MPP+

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