Cyanide‐induced parkinsonism

Uitti, Ryan J.; Rajput, A. H.; Ashenhurst, Edward M.; Rozdilsky, B.

doi:10.1212/wnl.35.6.921

Cited by 125 publications

(44 citation statements)

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“…This is the same abnormality reported in naturally occurring sporadic PD [85]. Further support for possible causation of PD by defects in electron transport chain is provided by the observation that a parkinsonian syndrome is sometimes a residual of cyanide poisoning, a known inhibitor of several functions of the electron transport chain [88].…”

Section: Abnormalities Of the Electron Transport Chain In Idiopathic Pdsupporting

confidence: 76%

Ubiquinone (Coenzyme Q<sub>10</sub>) and Mitochondria in Oxidative Stress of Parkinson’s Disease

et al. 2001

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Parkinson’s disease is the second most common neurodegenerative disorder after Alzheimer’s disease affecting approximately1% of the population older than 50 years. There is a worldwide increase in disease prevalence due to the increasing age of human populations. A definitive neuropathological diagnosis of Parkinson’s disease requires loss of dopaminergic neurons in the substantia nigra and related brain stem nuclei, and the presence of Lewy bodies in remaining nerve cells. The contribution of genetic factors to the pathogenesis of Parkinson’s disease is increasingly being recognized. A point mutation which is sufficient to cause a rare autosomal dominant form of the disorder has been recently identified in the α-synuclein gene on chromosome 4 in the much more common sporadic, or ‘idiopathic’ form of Parkinson’s disease, and a defect of complex I of the mitochondrial respiratory chain was confirmed at the biochemical level. Disease specificity of this defect has been demonstrated for the parkinsonian substantia nigra. These findings and the observation that the neurotoxin 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP), which causes a Parkinson-like syndrome in humans, acts via inhibition of complex I have triggered research interest in the mitochondrial genetics of Parkinson’s disease. Oxidative phosphorylation consists of five protein-lipid enzyme complexes located in the mitochondrial inner membrane that contain flavins (FMN, FAD), quinoid compounds (coenzyme Q₁₀, CoQ₁₀) and transition metal compounds (iron-sulfur clusters, hemes, protein-bound copper). These enzymes are designated complex I (NADH:ubiquinone oxidoreductase, EC 1.6. 5.3), complex II (succinate:ubiquinone oxidoreductase, EC 1.3.5.1), complex III (ubiquinol:ferrocytochrome c oxidoreductase, EC 1.10.2.2), complex IV (ferrocytochrome c:oxygen oxidoreductase or cytochrome c oxidase, EC 1.9.3.1), and complex V (ATP synthase, EC 3.6.1.34). A defect in mitochondrial oxidative phosphorylation, in terms of a reduction in the activity of NADH CoQ reductase (complex I) has been reported in the striatum of patients with Parkinson’s disease. The reduction in the activity of complex I is found in the substantia nigra, but not in other areas of the brain, such as globus pallidus or cerebral cortex. Therefore, the specificity of mitochondrial impairment may play a role in the degeneration of nigrostriatal dopaminergic neurons. This view is supported by the fact that MPTP generating 1-methyl-4-phenylpyridine (MPP⁺) destroys dopaminergic neurons in the substantia nigra. Although the serum levels of CoQ₁₀ is normal in patients with Parkinson’s disease, CoQ₁₀ is able to attenuate the MPTP-induced loss of striatal dopaminergic neurons.

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Section: Abnormalities Of the Electron Transport Chain In Idiopathic Pdsupporting

confidence: 76%

Ubiquinone (Coenzyme Q<sub>10</sub>) and Mitochondria in Oxidative Stress of Parkinson’s Disease

et al. 2001

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“…Cyanide toxicity can manifest as a Parkinson-like syndrome as a result of dopaminergic cell death in basal ganglia (Uitti et al, 1985). In the present study, cell death was observed in midbrains of mice repeatedly treated with cyanide as described by Mills et al (1999) with use of the same duration and dose of KCN treatment.…”

Section: Bnip3 Up-regulation In Mousesupporting

confidence: 62%

“…Cyanide is a classic mitochondrial toxicant associated with a secondary Parkinsonism that occurs after severe, acute intoxication (Uitti et al, 1985;Sarikaya et al, 2006). In sublethal toxicity, a postintoxication sequalae can manifest as akinesia and rigidity.…”

Section: Discussionmentioning

confidence: 99%

Cyanide-Induced Apoptosis of Dopaminergic Cells Is Promoted by BNIP3 and Bax Modulation of Endoplasmic Reticulum-Mitochondrial Ca²⁺ Levels

Zhang

Li²,

Leavesley³

et al. 2009

J Pharmacol Exp Ther

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Cyanide is a potent neurotoxicant that can produce dopaminergic neuronal death in the substantia nigra and is associated with a Parkinson-like syndrome. In this study involvement of Bcl-2/adenovirus E1B 19-kDa interacting protein 3 (BNIP3), a BH3-only Bcl-2 protein, in cyanide-induced death of dopaminergic cells was determined in mice and Mes 23.5 cells. Treatment of mice with cyanide up-regulated BNIP3 and Bax expression in tyrosine hydroxylase (TH)-positive cells of the substantia nigra, and progressive loss of TH-positive neurons was observed over a 9-day period. In Mes 23.5 dopaminergic cells, cyanide stimulated translocalization of BNIP3 to both endoplasmic reticulum (ER) and mitochondria. In ER, BNIP3 stimulated release of Ca 2ϩ into the cytosol, followed by accumulation of mitochondrial Ca 2ϩ , resulting in reduction of mitochondrial membrane potential (⌬ m ) and eventually cell death. Cyanide also activated Bax to colocalize with BNIP3 in ER and mitochondria. Forced overexpression of BNIP3 activated Bax, whereas gene silencing reduced Bax activity. Knockdown of Bax expression by small interfering RNA blocked the BNIP3-mediated changes in ER and mitochondrial Ca 2ϩ to block cyanide-induced mitochondrial dysfunction and cell death. These findings show that BNIP3-mediates cyanide-induced dopaminergic cell death through a Bax downstream signal that mobilizes ER Ca 2ϩ stores, followed by mitochondrial Ca 2ϩ overload.

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“…Some sequelae of cyanide toxicity in humans have been associated with damage to the basal ganglia, including Parkinsonian symptoms (Finelli, 1981;Uitti et al, 1985;Carella et al, 1988;Rosemberg et al, 1989;Feldman and Feldman, 1990;Messing, 1991), phobic anxiety (Nicholson and Vincenti, 1994) and psychosis (El Ghawabi et al, 1975;Kales et al, 1997). Furthermore, cyanide intoxication has been linked to personality change in a man (Uitti et al, 1985).…”

Section: Discussionmentioning

confidence: 99%

Clinical and pathological effects of short-term cyanide repeated dosing to goats

Soto-Blanco¹,

Stegelmeier²,

Górniak³

2005

J. Appl. Toxicol.

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The purpose of this work is to determine and describe the effects of subacute cyanide toxicity to goats. Eight female goats were divided into two groups. The first group of five animals was treated with 8.0 mg KCN kg(-1) body weight day(-1) for seven consecutive days. The second group of three animals was treated with water as controls. Complete physical examination, including observation for behavior changes, was conducted before and after dosing. One treated animal was euthanized immediately after dosing. Later, two of the remaining treated animals and a control goat were euthanized after a 30-day recovery period. Euthanized animals were necropsied and tissues were collected and prepared for histologic studies. Clinical signs in treated goats were transient and included depression and lethargy, mild hyperpnea and hyperthermia, arrhythmias, abundant salivation, vocalizations, expiratory dyspnea, jerky movements and head pressing. Two goats developed convulsions after day 3 of treatment. One animal developed more permanent behavioral changes as she became less dominant and aggressive. Histologic changes included mild hepatocellular vacuolation and degeneration, mild vacuolation and swelling of the proximal convoluted tubules of the kidneys and spongiosis of the white matter (status spongiosis) of the cerebral white tracts, internal capsule, cerebellar peduncles, spinal cord and peripheral nerves. In summary, sub-lethal cyanide intoxication in goats resulted in behavioral changes, and during the treatment period animals showed delayed signs of toxicity. Significant histologic lesions in goats were observed and need to be characterized further.

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Cyanide‐induced parkinsonism

Cited by 125 publications

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Ubiquinone (Coenzyme Q<sub>10</sub>) and Mitochondria in Oxidative Stress of Parkinson’s Disease

Ubiquinone (Coenzyme Q<sub>10</sub>) and Mitochondria in Oxidative Stress of Parkinson’s Disease

Cyanide-Induced Apoptosis of Dopaminergic Cells Is Promoted by BNIP3 and Bax Modulation of Endoplasmic Reticulum-Mitochondrial Ca²⁺ Levels

Clinical and pathological effects of short-term cyanide repeated dosing to goats

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Cyanide‐induced parkinsonism

Cited by 125 publications

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Ubiquinone (Coenzyme Q<sub>10</sub>) and Mitochondria in Oxidative Stress of Parkinson’s Disease

Ubiquinone (Coenzyme Q<sub>10</sub>) and Mitochondria in Oxidative Stress of Parkinson’s Disease

Cyanide-Induced Apoptosis of Dopaminergic Cells Is Promoted by BNIP3 and Bax Modulation of Endoplasmic Reticulum-Mitochondrial Ca2+ Levels

Clinical and pathological effects of short-term cyanide repeated dosing to goats

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Cyanide-Induced Apoptosis of Dopaminergic Cells Is Promoted by BNIP3 and Bax Modulation of Endoplasmic Reticulum-Mitochondrial Ca²⁺ Levels