Early α-synuclein lipoxidation in neocortex in Lewy body diseases

Dalfó, Esther; Ferrer, Isidre

doi:10.1016/j.neurobiolaging.2006.10.022

Cited by 68 publications

(39 citation statements)

References 45 publications

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“…α-Synuclein isolated postmortem from the frontal cortex and SN of PD patients has been shown to contain this modification. The extent to which this is a PD specific modification is unknown as one control cortex sample and one control SN sample were found to have α-synuclein containing MDALys [61].…”

Section: α-Synucleinmentioning

confidence: 99%

Oxidative and nitrative protein modifications in Parkinson's disease

Danielson

Andersen

2008

Free Radical Biology and Medicine

184

119

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Parkinson's disease (PD) is a complex neurodegenerative syndrome likely involving contributions from various factors in individuals including genetic susceptibility, exposure to environmental toxins, and the aging process itself. Increased oxidative stress appears to be a common causative aspect involved in the preferential loss of dopaminergic neurons in a region of the brain prominently affected by the disorder, the substantia nigra (SN). Loss of dopaminergic SN neurons is responsible for the classic clinical motor symptoms associated with PD. Several oxidative and nitrative posttranslational modifications (PTMs) have been identified on proteins pertinent to PD that may affect this or other aspects of disease progression. In this review, we discuss several examples of such PTMs to illustrate their potential consequences in terms of initiation or progression of PD neuropathophysiology.

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Section: α-Synucleinmentioning

confidence: 99%

Oxidative and nitrative protein modifications in Parkinson's disease

Danielson

Andersen

2008

Free Radical Biology and Medicine

184

119

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“…4-Hydroxy-2-nonenal (HNE)-modified proteins are accumulated in the brainstem and cortical-type Lewy bodies in PD and DLB (5,52), as well as in glial and neuronal inclusion bodies in multiple system atrophy (46). Additionally, the modification of a-synuclein by malondialdehyde, another common lipid peroxidation product, was observed in the frontal cortices and the substantia nigra in PD and DLB patients (7). Lipoxidative damages represented by protein adducts with HNE and malondialdehyde were shown to be increased in incidental Lewy body disease, thereby suggesting that lipid peroxidation and the resultant protein modification occur in the early stages of parkinsonian neuropathology (8).…”

mentioning

confidence: 99%

Lipid Peroxidation Product 4-Hydroxy-2-Nonenal Promotes Seeding-Capable Oligomer Formation and Cell-to-Cell Transfer of α-Synuclein

Bae

Park

et al. 2013

Antioxidants & Redox Signaling

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Aims: Abnormal accumulation of a-synuclein aggregates is one of the key pathological features of many neurodegenerative movement disorders and dementias. These pathological aggregates propagate into larger brain regions as the disease progresses, with the associated clinical symptoms becoming increasingly severe and complex. However, the factors that induce a-synuclein aggregation and spreading of the aggregates remain elusive. Herein, we have evaluated the effects of the major lipid peroxidation byproduct 4-hydroxy-2-nonenal (HNE) on a-synuclein oligomerization and cell-to-cell transmission of this protein. Results: Incubation with HNE promoted the oligomerization of recombinant human a-synuclein via adduct formation at the lysine and histidine residues. HNE-induced a-synuclein oligomers evidence a little b-sheet structure and are distinct from amyloid fibrils at both conformation and ultrastructure levels. Nevertheless, the HNE-induced oligomers are capable of seeding the amyloidogenesis of monomeric a-synuclein under in vitro conditions. When neuronal cells were treated with HNE, both the translocation of a-synuclein into vesicles and the release of this protein from cells were increased. Neuronal cells can internalize HNE-modified a-synuclein oligomers, and HNE treatment increased the cell-to-cell transfer of a-synuclein proteins. Innovation and Conclusion: These results indicate that HNE induces the oligomerization of a-synuclein through covalent modification and promotes the cell-to-cell transfer of seedingcapable oligomers, thereby contributing to both the initiation and spread of a-synuclein aggregates. Antioxid. Redox Signal. 18,[770][771][772][773][774][775][776][777][778][779][780][781][782][783]

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“…Moreover, it demonstrates that aSyn lipoxidation is an early event in LBDs which precedes aSyn solubility modification and aggregation, and formation of Lewy bodies and neuritis [61]. It also been found that the human brain cortex, mitochondrial oxygen uptake and complex I activity were significantly lower in DLB, comparing to healthy controls, whereas oxidative damage and mtNOS activity, cytochrome content, expression of Mn-SOD and mitochondrial mass were significantly higher in the frontal cortex in DLB [62].…”

Section: Definition and Pathology Of Dementia Withmentioning

confidence: 82%

Recent progress and concerns in dementia: Distinguishing Alzheimer's disease and dementia with Lewy bodies via biochemical markers in the cerebrospinal fluid

Mao¹

2012

ABC

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Dementia is mainly a neurodegenerative disorder involved in several systems, including central nervous system, endocrinology/metabolism system and circulatory system. Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) are the most common forms of the dementia, accounting for 60% -80% and 10% -20% of all cases, respectively. DLB is defined by widespread neocortical, limbic and brainstem Lewy bodies but frequently accompanied by variable levels of AD pathology. This pathological and clinical overlap makes their differential diagnosis complicated. Recent advances in the identification of disease biomarkers now make it possible to detect and distinguish their pathology in the early or preclinical stage of the diseases, even in cognitively normal individuals. In addition to the key biomarkers (amyloid β or Aβ, tau and α-synuclein), neurotrophins such as cocaineand amphetamine-regulated transcript (CART) have also drawn attention due to their expressions and functions. This article summarizes the progress in the definition, pathology and diagnosis of dementia, with a focus on potential biochemical markers in the cerebrospinal fluid (CSF) in the differential diagnosis of the main forms of dementia. To prediction or early diagnosis of dementia, the role of specific and sensitive CSF biomarkers seems to be crucial in a routine clinical setting. The concerns and challenges in the biomarker field are also discussed.

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Early α-synuclein lipoxidation in neocortex in Lewy body diseases

Cited by 68 publications

References 45 publications

Oxidative and nitrative protein modifications in Parkinson's disease

Oxidative and nitrative protein modifications in Parkinson's disease

Lipid Peroxidation Product 4-Hydroxy-2-Nonenal Promotes Seeding-Capable Oligomer Formation and Cell-to-Cell Transfer of α-Synuclein

Recent progress and concerns in dementia: Distinguishing Alzheimer's disease and dementia with Lewy bodies via biochemical markers in the cerebrospinal fluid

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