Manganese-Induced Parkinsonism due to Ephedrone Abuse

Sikk, Katrin; Haldre, Sulev; Aquilonius, Sten–Magnus; Taba, Pille

doi:10.4061/2011/865319

Cited by 52 publications

(59 citation statements)

References 32 publications

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“…Environmental risk factors, including prolonged pesticide exposure and lead or manganese intoxication, have been observed to cause parkinsonian symptoms (5)(6)(7)(8). Altered zinc, copper, and iron levels have been found specifically in the substantia nigra of PD patients compared with controls (9).…”

Section: Parkinson Disease (Pd)mentioning

confidence: 99%

Parkinson Disease Protein DJ-1 Binds Metals and Protects against Metal-induced Cytotoxicity

Björkblom

Adilbayeva

Maple‐Grødem

et al. 2013

Journal of Biological Chemistry

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The progressive loss of motor control due to reduction of dopamine-producing neurons in the substantia nigra pars compacta and decreased striatal dopamine levels are the classically described features of Parkinson disease (PD). Neuronal damage also progresses to other regions of the brain, and additional nonmotor dysfunctions are common. Accumulation of environmental toxins, such as pesticides and metals, are suggested risk factors for the development of typical late onset PD, although genetic factors seem to be substantial in early onset cases. Mutations of DJ-1 are known to cause a form of recessive early onset Parkinson disease, highlighting an important functional role for DJ-1 in early disease prevention. This study identifies human DJ-1 as a metal-binding protein able to evidently bind copper as well as toxic mercury ions in vitro. The study further characterizes the cytoprotective function of DJ-1 and PD-mutated variants of DJ-1 with respect to induced metal cytotoxicity. The results show that expression of DJ-1 enhances the cells' protective mechanisms against induced metal toxicity and that this protection is lost for DJ-1 PD mutations A104T and D149A. The study also shows that oxidation site-mutated DJ-1 C106A retains its ability to protect cells. We also show that concomitant addition of dopamine exposure sensitizes cells to metal-induced cytotoxicity. We also confirm that redox-active dopamine adducts enhance metal-catalyzed oxidation of intracellular proteins in vivo by use of live cell imaging of redox-sensitive S3roGFP. The study indicates that even a small genetic alteration can sensitize cells to metal-induced cell death, a finding that may revive the interest in exogenous factors in the etiology of PD. Parkinson disease (PD)3 is the second most common neurodegenerative disease, classically described as a progressive movement disorder, and with increased prevalence in the aging population. Selective degeneration of dopamine-producing neurons in the substantia nigra pars compacta (SNpc) and depletion of striatal dopamine levels are the cardinal features of PD (1). It has been estimated that 50 -60% of the SNpc dopaminergic neurons are irreversibly lost, and about 80 -85% of the dopamine content of the striatum is depleted by the time of clinical diagnosis (2). However, there are also widespread alterations in other brain regions observed in a predominant caudal to rostral progression that may influence the development of non-motor symptoms, such as pain, sleep disorders, cognitive decline, or depression (3, 4). Because the progression of the disease is slow, but irreversible, the underlying factors resulting in cell death need to be clarified to enable new treatment strategies for the affected patients.PD etiology remains obscure and appears in most instances sporadic in nature. Environmental risk factors, including prolonged pesticide exposure and lead or manganese intoxication, have been observed to cause parkinsonian symptoms (5-8). Altered zinc, copper, and iron levels have been found specifi...

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Section: Parkinson Disease (Pd)mentioning

confidence: 99%

Parkinson Disease Protein DJ-1 Binds Metals and Protects against Metal-induced Cytotoxicity

Björkblom

Adilbayeva

Maple‐Grødem

et al. 2013

Journal of Biological Chemistry

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“…Procedures of this type make it impossible to completely remove manganese or chromium ions from the mixture; therefore, compounds containing these elements can enter the human body. Literature data include reports linking the presence of manganese ions delivered in such a manner with Parkinson's disease, possibly as a causative factor [7,8]. Organic synthetic procedures for obtaining ephedrone from ephedrine and its analogues have also been reported [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Crystal structures and other properties of ephedrone (methcathinone) hydrochloride, N-acetylephedrine and N-acetylephedrone

et al. 2018

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Purpose Three compounds obtained from ephedrine were identified and characterized by various instrumental analytical methods. Ephedrone (methcathinone) hydrochloride and its fundamental derivatives N-acetylephedrine and N-acetylephedrone were analyzed as precursors of a cathinone derivative. Methods The obtained samples were analyzed by gas chromatography coupled with mass spectrometry, nuclear magnetic resonance spectroscopy, infrared and Raman spectroscopy, and X-ray crystallography. Results The three compounds were confirmed as: N-methyl-2-amino-1-phenylpropan-1-one (methcathinone) hydrochloride, N-acetyl-N-methyl-2-amino-1-phenylpropan-1-one (cathinone derivative), and N-acetyl-N-methyl-2-amino-1-phenylpropan-1-ol (acetyl derivative of ephedrine). Conclusions X-ray crystallography is especially useful for identifying the new designer drugs and their different precursor forms.

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“…These neurologic symptoms are collectively termed as manganism and are often seen ephedrone abusers 98,99 and have been also described in welders who work poorly ventilated places. 100 Symptoms are usually progressive despite cessation of manganese exposure.…”

Section: Movement Disorders In Systemic Intoxications Manganesementioning

confidence: 97%