Elevated plasma homocysteine levels in L-dopa-treated Parkinson's disease patients with dyskinesias

Zoccolella, Stefano; Lamberti, Paolo; Iliceto, Giovanni; Dell’Aquila, Claudia; Diroma, Cosimo; Fraddosio, Angela; Lamberti, S.; Armenise, Elio; Defazio, Giovanni; Mari, Michele; Livrea, Paolo

doi:10.1515/cclm.2006.143

Cited by 24 publications

(22 citation statements)

References 14 publications

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“…Following the in vitro and in vivo observations on the toxic effects of Hcy on dopaminergic neurons in the substantia nigra, some authors have suggested that HHcy associated with LD may play a role in the progression of PD and the development of motor complications and that dyskinesias and motor fluctuations may be due to the toxic effects of Hcy [7, 12]. …”

Section: Discussionmentioning

confidence: 99%

“…Hence, it was suggested that plasma HHcy may play a role in the development of dyskinesias due to the toxic effects of Hcy on dopaminergic and nondopaminergic neurons [7]. …”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, Hcy may be associated with dyskinesias, which is an indicator of possible neurodegeneration due to the disruption of the balance of striatal activity [6, 7]. …”

Section: Introductionmentioning

confidence: 99%

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The Effect of Hyperhomocysteinemia on Motor Symptoms, Cognitive Status, and Vascular Risk in Patients with Parkinson’s Disease

Koçer

Güven

Conkbayir

et al. 2016

Parkinson's Disease

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Factors related with hyperhomocysteinemia (HHcy) and the impact of HHcy in Parkinson's disease (PD) are not well understood. We investigated the factors associated with increased levels of homocysteine (Hcy) and the relationship between HHcy and motor symptoms, cognitive status, and vascular risk in patients with Parkinson's disease. Among 60 patients (29 males, 48.3%) with PD, the stage of the disease, the severity of clinical symptoms, and the patients' cognitive status were measured using a modified Hoehn and Yahr Staging Scale (mHY), Unified Parkinson's Disease Rating Scale (UPDRS) II and III, and Mini-Mental State Examination (MMSE), respectively. Patients were also noted for having dyskinesia and hallucinations. Serum vitamin B12, folic acid, and plasma Hcy levels were measured. Furthermore, the presence of vascular risk factors was recorded. Finally, we investigated carotid artery intima-media thickening and stenosis using colour Doppler ultrasonography as well as the presence of ischemic lesions using brain imaging techniques. Plasma Hcy levels were higher with advanced age and in males. In addition, there was an inverse relationship between Hcy and vitamin B12 levels. There was no correlation between HHcy and the stage of the disease, severity of motor symptoms, cognitive status as assessed by the MMSE, vascular risk factors, carotid artery atherosclerotic findings, and ischemic brain lesions. Plasma Hcy levels may rise due to several factors in PD. However, the resulting HHcy has no significant effect on the clinical picture in terms of motor features, cognitive status, and vascular diseases.

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Section: Discussionmentioning

confidence: 99%

“…Hence, it was suggested that plasma HHcy may play a role in the development of dyskinesias due to the toxic effects of Hcy on dopaminergic and nondopaminergic neurons [7]. …”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The Effect of Hyperhomocysteinemia on Motor Symptoms, Cognitive Status, and Vascular Risk in Patients with Parkinson’s Disease

Koçer

Güven

Conkbayir

et al. 2016

Parkinson's Disease

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“…These implications may result in the complications seen in PD therapy, such as the effect of high levels of Hcy on the reactivity of patients to L-dopa and dopamine agonists commonly used in the treatment of PD. On the other hand, the clinical observations of dyskinesia that becomes gradually higher in PD patients with elevated Hcy may suggest that Hcy acts in the opposite manner (hypersensitivity of receptors) [56]. …”

Section: Hcy In Pd: Possible Mechanisms Of Injurymentioning

confidence: 99%

Homocysteine Level and Mechanisms of Injury in Parkinson's Disease as Related to MTHFR, MTR, and MTHFD1 Genes Polymorphisms and LDopa Treatment

Różycka

Jagodzińśki

Kozubski

et al. 2014

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An elevated concentration of total homocysteine (tHcy) in plasma and cerebrospinal fluid is considered to be a risk factor for Alzheimer's disease (AD) and Parkinson's disease (PD). Homocysteine (Hcy) levels are influenced by folate concentrations and numerous genetic factors through the folate cycle, however, their role in the pathogenesis of PD remains controversial. Hcy exerts a neurotoxic action and may participate in the mechanisms of neurodegeneration, such as excitotoxicity, oxidative stress, calcium accumulation, and apoptosis. Elevated Hcy levels can lead to prooxidative activity, most probably through direct interaction with N-methyl-D-aspartate (NMDA) receptors and sensitization of dopaminergic neurons to age-related dysfunction and death. Several studies have shown that higher concentration of Hcy in PD is related to long-term administration of levodopa (L-dopa). An elevation of plasma tHcy levels can also reflect deficiencies of cofactors in remethylation of Hcy to methionine (Met) (folates and vitamin B12) and in its transsulfuration to cysteine (Cys) (vitamin B6). It is believed that the increase in the concentration of Hcy in PD can affect genetic polymorphisms of the folate metabolic pathway genes, such as MTHFR (C677T, A1298C and G1793A), MTR (A2756G), and MTHFD1 (G1958A), whose frequencies tend to increase in PD patients, as well as the reduced concentration of B vitamins. In PD, increased levels of Hcy may lead to dementia, depression and progression of the disease.

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“…Depression und visuelle Funktionsstörungen auslöst und zur Ausprägung einer allgemeinen Gefäßsklerose führen kann. Homocystein wird bei Patienten mit L-Dopa-Therapie deutlich erhöht im Serum gefunden[6]. Der unzureichende Abbau von Pestiziden (z.B.…”

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Ganzheitliche Diagnostik und Therapie des Parkinson-Syndroms

Kersten¹

2009

Komplementäre und Integrative Medizin

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Elevated plasma homocysteine levels in L-dopa-treated Parkinson's disease patients with dyskinesias

Abstract: Our results raise the possibility that Hcy plays a role in the development of dyskinesias, through its toxic effects on both dopaminergic neurons and non-substantia nigra, non-dopaminergic neurons.

Cited by 24 publications

References 14 publications

The Effect of Hyperhomocysteinemia on Motor Symptoms, Cognitive Status, and Vascular Risk in Patients with Parkinson’s Disease

The Effect of Hyperhomocysteinemia on Motor Symptoms, Cognitive Status, and Vascular Risk in Patients with Parkinson’s Disease

Homocysteine Level and Mechanisms of Injury in Parkinson's Disease as Related to MTHFR, MTR, and MTHFD1 Genes Polymorphisms and LDopa Treatment

Ganzheitliche Diagnostik und Therapie des Parkinson-Syndroms

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