Genetic influence on the development of Parkinson’s disease

Rieß, Olaf; Kühn, Wilfried; Krüger, Rejko

doi:10.1007/pl00007764

Cited by 25 publications

(17 citation statements)

References 43 publications

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“…In addition, dysfunction of the autonomic nervous system as well as subtle cognitive impairment and depression are observed in a large percentage of patients [119]. Since it affects approximately 0.5% of the population over 50 years of age, PD is expected to form a steadily growing socio-economic burden for the society [120].…”

Section: Oxidative Stress In Parkinson's Diseasementioning

confidence: 99%

The Nrf2-ARE Signalling Pathway: Promising Drug Target to Combat Oxidative Stress in Neurodegenerative Disorders

Muiswinkel¹,

2005

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A large body of evidence indicates that oxidative stress is a salient pathological feature in many neurodegenerative diseases, including Amyotrophic lateral sclerosis, Alzheimer's disease, and Parkinson's disease. In addition to signs of systemic oxidative stress, at the biochemical and neuropathological level, neuronal degeneration in these disorders has been shown to coincide with several markers of oxidative damage to lipids, nucleic acids, and proteins in affected brain regions. Neuroinflammatory processes, often associated with the induction of free radical generating enzymes and the accumulation of reactive astrocytes and microglial cells, are considered as a major source of oxidative stress. Given the pathogenic impact of oxidative stress and neuroinflammation, therapeutic strategies aimed to blunt these processes are considered an effective way to confer neuroprotection. Recently, the nuclear transcription factor Nrf2, that binds to the antioxidant response element (ARE) in gene promoters, has been reported to constitute a key regulatory factor in the co-ordinate induction of a battery of endogenous cytoprotective genes, including those encoding for both antioxidant- and anti-inflammatory proteins. In the present review, besides discussing recent evidence underscoring the thesis that the Nrf2-ARE signalling pathway is an attractive therapeutic target for neurodegenerative diseases, we advocate the view that chemopreventive agents might be suitable candidates to serve as lead compounds for the development of a new class of neuroprotective drugs.

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Section: Oxidative Stress In Parkinson's Diseasementioning

confidence: 99%

The Nrf2-ARE Signalling Pathway: Promising Drug Target to Combat Oxidative Stress in Neurodegenerative Disorders

Muiswinkel¹,

2005

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“…Abnormal accumulation of NFs in neurons is associated with other neurodegenerative diseases, such as Alzheimer's disease (AD) (12) and amyotrophic lateral sclerosis (ALS) (13). Recent progress in PD research indicates that PD might be caused by protein aggregation due to aberrant protein folding or disturbed protein degradation (14). However, the factors and mechanisms that aggregate NFs remain to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

Salsolinol, a tetrahydroisoquinoline-derived neurotoxin, induces oxidative modification of neurofilament-L: protection by histidyl dipeptides

Kang¹

2012

BMB Reports

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Salsolinol (1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline) is a compound derived from dopamine metabolism and is capable of causing dopaminergic neurodegeneration. Oxidative modification of neurofilament proteins has been implicated in the pathogenesis of neurodegenerative disorders. In this study, oxidative modification of neurofilament-L (NF-L) by salsolinol and the inhibitory effects of histidyl dipeptides on NF-L modification were investigated. When NF-L was incubated with 0.5 mM salsolinol, the aggregation of protein was increased in a time-dependent manner. We also found that the generation of hydroxyl radicals (•OH) was linear with respect to the concentrations of salsolinol as a function of incubation time. NF-L exposure to salsolinol produced losses of glutamate, lysine and proline residues. These results suggest that the aggregation of NF-L by salsolinol may be due to oxidative damage resulting from free radicals. Carnosine, histidyl dipeptide, is involved in many cellular defense processes, including free radical detoxification.

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“…Recent progress in PD research indicates that PD might be caused by protein aggregation due to aberrant protein folding or disturbed protein degradation. 3 Lewy bodies (LBs) are cytoplasmic inclusions that are present consistently and with greatest frequency in neurons of the substantia nigra and locus ceruleus of patients with PD. 4 Neurofilament proteins have been identified immunohistochemically as the major protein components of LB filament.…”

Section: Introductionmentioning

confidence: 99%

Oxidative Modification of Neurofilament-L Induced by Endogenous Neurotoxin, Salsolinol

Kang¹

2011

Bulletin of the Korean Chemical Society

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The endogenous neurotoxin, 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (salsolinol), has been considered a potential causative factor for the pathogenesis of Parkinson's disease (PD). In this study, we examined oxidative modification of neurofilament-L (NF-L) induced by salsolinol. When disassembled NF-L was incubated with salsolinol, the aggregation of protein was increased with the concentration of sasolinol. The formation of carbonyl compound was obtained in salsolinol-mediated NF-L aggregates. This process was protected by free radical scavengers, such as N-acetyl-L-cysteine and glutathione. These results suggest that the aggregation of NF-L is mediated by salsolinol via the generation of free radicals. We also investigated the effects of copper ion on salsolinol-mediated NF-L modification. In the presence of copper ions, salsolinol enhanced the modification of NF-L. We suggest that salsolinol might be related to abnormal aggregation of NF-L which may be involved in the pathogenesis of neurodegenerative diseases and related disorders.

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Genetic influence on the development of Parkinson’s disease

Cited by 25 publications

References 43 publications

The Nrf2-ARE Signalling Pathway: Promising Drug Target to Combat Oxidative Stress in Neurodegenerative Disorders

The Nrf2-ARE Signalling Pathway: Promising Drug Target to Combat Oxidative Stress in Neurodegenerative Disorders

Salsolinol, a tetrahydroisoquinoline-derived neurotoxin, induces oxidative modification of neurofilament-L: protection by histidyl dipeptides

Oxidative Modification of Neurofilament-L Induced by Endogenous Neurotoxin, Salsolinol

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