The Etiopathogenesis of Parkinson Disease and Suggestions for Future Research. Part I

Litvan, Irene; Chesselet, Marie Françoise; Gasser, Thomas; Monte, Donato A. Di; Parker, Davis; Hagg, Theo; Hardy, John; Jenner, Peter; Myers, Richard H.; Price, Donald L.; Hallett, Mark; Langston, W.J.; Lang, Anthony E.; Halliday, Glenda M.; Rocca, Walter A.; Duyckaerts, Charles; Dickson, Dennis W.; Ben‐Shlomo, Yoav; Goetz, Christopher G.; Melamed, Eldad

doi:10.1097/nen.0b013e3180415e42

Cited by 110 publications

(81 citation statements)

References 78 publications

(70 reference statements)

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“…Parkinson's disease afflicts many individuals but an effective disease management or a prevention strategy is unavailable and the underlying molecular etiology is not clear (Dawson and Dawson, 2003;Lee and Trojanowski, 2006;Litvan et al, 2007a). Several molecular culprits of PD have been suggested, including ␣-synuclein, normally a presynaptic protein (Dawson and Dawson, 2003;Lee and Trojanowski, 2006).…”

Section: Discussionmentioning

confidence: 99%

“…The molecular mechanism of PD remains elusive (Dawson and Dawson, 2003;Lee and Trojanowski, 2006;Litvan et al, 2007a), but one important factor in the disease pathogenesis is oxidative stress (Jenner, 2003;Litvan et al, 2007b), which can promote oxidation of cell constituents, including amino acids. Among them, cysteine and methionine are particularly susceptible to oxidation.…”

Section: Introductionmentioning

confidence: 99%

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Methionine Sulfoxide Reductase A and a Dietary SupplementS-Methyl-L-Cysteine Prevent Parkinson's-Like Symptoms

Wassef¹,

Haenold²,

Hansel³

et al. 2007

J. Neurosci.

114

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Parkinson's disease (PD), a common neurodegenerative disease, is caused by loss of dopaminergic neurons in the substantia nigra. Although the underlying cause of the neuronal loss is unknown, oxidative stress is thought to play a major role in the pathogenesis of PD. The amino acid methionine is readily oxidized to methionine sulfoxide, and its reduction is catalyzed by a family of enzymes called methionine sulfoxide reductases (MSRs). The reversible oxidation-reduction cycle of methionine involving MSRs has been postulated to act as a catalytic antioxidant system protecting cells from oxidative damage. Here, we show that one member of the MSR family, MSRA, inhibits development of the locomotor and circadian rhythm defects caused by ectopic expression of human ␣-synuclein in the Drosophila nervous system. Furthermore, we demonstrate that one way to enhance the MSRA antioxidant system is dietary supplementation with S-methyl-L-cysteine (SMLC), found abundantly in garlic, cabbage, and turnips. SMLC, a substrate in the catalytic antioxidant system mediated by MSRA, prevents the ␣-synuclein-induced abnormalities. Therefore, interventions focusing on the enzymatic reduction of oxidized methionine catalyzed by MSRA represent a new prevention and therapeutic approach for PD and potentially for other neurodegenerative diseases involving oxidative stress.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Methionine Sulfoxide Reductase A and a Dietary SupplementS-Methyl-L-Cysteine Prevent Parkinson's-Like Symptoms

Wassef¹,

Haenold²,

Hansel³

et al. 2007

J. Neurosci.

114

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“…Idiopathic Parkinson's disease (PD) is characterized by the selective loss of dopamine neurons in the substantia nigra and is responsive to the exogenous administration of levodopa (L-DOPA) [Litvan et al, 2007]. The neurons that degenerate contain the rate-limiting enzyme for dopamine synthesis, tyrosine hydroxylase (TH).…”

Section: Introductionmentioning

confidence: 99%

Haplotype analysis of the IGF2‐INS‐TH gene cluster in Parkinson's disease

Sutherland

Mellick

Newman

et al. 2008

American J of Med Genetics Pt B

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Idiopathic Parkinson's disease is a common movement disorder characterized by a loss of dopaminergic neurons in the substantia nigra. Its pathogenesis is postulated to involve complex interactions between genetic susceptibility and environmental exposures. The IGF2-INS-TH gene cluster on the telomeric end of human chromosome 11 is a gene rich region expressing several proteins important for dopamine neuron homeostasis. We used a haplotyping approach to determine whether common genetic variation in the IGF2-INS-TH cluster influences the risk of idiopathic Parkinson's disease in a Caucasian case-control group recruited from Brisbane, Australia. Three tagging polymorphisms, the SNPs, rs680 and rs689 and the microsatellite, HUMTH01, were genotyped in 215 cases and 215 age- and gender-matched controls. Eight common haplotypes accounted for 91% of the genetic variation in our control group and one haplotype, IGF2-INS-TH*6, was significantly under-represented among the cases with idiopathic Parkinson's disease (OR = 0.42, 95% CI = 0.25-0.72, P-value = 0.001). Analysis of the individual polymorphisms showed that the IGF2-rs680 alternate 'A' allele accounted for the majority of the protective effect. Our findings suggest that common genetic variants in the IGF2-INS-TH cluster modify susceptibility to idiopathic Parkinson's disease.

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“…Nörodejeneratif bir hastalık olan İdiyopatik Parkinson hastalığı (İPH) santral sinir sisteminde spesifik alanların progressif nöronal dejenerasyonu ile karakterizedir (1,2). Nörodejeneratif hastalıkların patogenezinde eksitotoksik mekanizmalar, oksidatif hasar, enflamasyon, mitokondriyal enerji metabolizması ve intrasellüler kalsiyum dengesindeki bozuklukların etken olabileceğine ilişkin bilgiler mevcuttur.…”

Section: Introductionunclassified

The Role of Ceruloplasmin in Neurodegeneration in Parkinson’s Disease

Gürer¹,

Aydın²,

Gökçe³

et al. 2016

tnd

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Amaç: İdiyopatik Parkinson hastalığında (İPH) oksidatif stres nöronal hücre ölümü üzerinde majör role sahiptir. Serüloplazmin ferrooksidaz aktivitesi ile ferröz demiri ferrik forma okside eder ve böylece hücrenin DNA, lipid ve protein bileşenlerini oksidatif hasardan korur. Bizim çalışmamızda proton manyetik rezonans spektroskopi (H-1 MRS) ile serüloplazmin eksikliğinin nörodejenerasyon üzerindeki etkisi araştırılmıştır. Gereç ve Yöntem: İPH tanılı 23 hasta ve 12 sağlıklı kontrol olguda iki yanlı putamen tek voksel H-1 MRS yöntemiyle incelendi. Her iki grupta N-asetil aspartat (NAA), kreatin (Cr) ve kolin (Cho) pik değerleri ve serum serüloplazmin düzeyleri belirlendi. Bulgular: İPH hastalarında semptomatik ekstremitenin kontralateral (KL) putaminal bölge NAA/Cho ve NAA/Cr oranı kontrol grubuna kıyasla anlamlı derecede düşüktü. Ayrıca İPH grubunda KL NAA/Cho ve NAA/Cr oranları ipsilateraline (İL) göre anlamlı derecede düşüktü (p<0,001). Semptomatik ekstremitenin İL putaminal bölgeye ait metabolit oranları karşılaştırıldığında sağlıklı kontrol ile İPH grubu arasında anlamlı fark saptanmadı. Serum serüloplazmin seviyeleri kontrol grubu ile karşılaştırıldığında İPH grubunda anlamlı derecede düşük saptandı (p<0,001). İPH grubunda KL putaminal NAA/Cho oranı ile serüloplazmin seviyeleri arasında anlamlı korelasyon saptandı (p=0,011). Sonuç: Çalışmamızda saptanan serum serüloplazmin düşüklüğü ile KL putamen NAA/Cho oranı arasındaki bu korelasyon serbest radikal aracılı nöronal hücre ölümünde serüloplazmin yetersizliğinin katkıda bulunabileceği hipotezini desteklemektedir. Anahtar Kelimeler: İdiyopatik Parkinson hastalığı, proton manyetik rezonans spektroskopi, serüloplazmin Objective: Oxidative stress has been implicated to play a major role in the neuronal cell death in idiopathic Parkinson's disease (IPD). Ceruloplasmin is a ferroxidase that oxidizes toxic ferrous iron to its nontoxic ferric form and thus helps prevent oxidative damage to proteins, lipids, and DNA. The aim of this study was to determine the serum ceruloplasmin levels in patients with IPD and evaluate its role in neurodegeneration using hydrogen proton magnetic resonance spectroscopic imaging (H-1 MRSI). Materials and Methods: Twenty-three patients with the IPD and 12 healthy controls were studied using single-voxel H-1 MRSI of the bilateral putamen. The peak ratios of N-acetyl aspartate (NAA) to creatinine (Cr) and choline (Cho) were measured in both groups and serum ceruloplasmin levels were detected. Results: Compared with the controls, the ratios of NAA/Cho and NAA/Cr in putamen contralateral (CL) to the symptomatic limbs were significantly lower in patients with IPD. Also in the IPD group, CL NAA/Cho and NAA/Cr ratios were significantly lower than the ipsilateral (IL) values (p<0.001). There was no significant difference between ratios of metabolites in putamen IL to the symptomatic limbs in the IPD group compared with the healthy controls. The mean serum ceruloplasmin level of IPD patients was significantly lower than that of the control group (...

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The Etiopathogenesis of Parkinson Disease and Suggestions for Future Research. Part I

Cited by 110 publications

References 78 publications

Methionine Sulfoxide Reductase A and a Dietary SupplementS-Methyl-L-Cysteine Prevent Parkinson's-Like Symptoms

Methionine Sulfoxide Reductase A and a Dietary SupplementS-Methyl-L-Cysteine Prevent Parkinson's-Like Symptoms

Haplotype analysis of the IGF2‐INS‐TH gene cluster in Parkinson's disease

The Role of Ceruloplasmin in Neurodegeneration in Parkinson’s Disease

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