Parkinsonian Syndrome Caused by 1-Methyl-4-Phenyl-1,2,3,6-tetrahydropyridine (MPTP) in Man and Animals

Jenner, Peter; Marsden, C. D.

doi:10.1007/978-1-349-08759-4_9

Cited by 5 publications

(3 citation statements)

References 90 publications

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“…Given its anti-inflammatory effect, the efficacy of PEA in controlling neurodegeneration associated with neuroinflammation has been evaluated in the animal model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) injections. In this model, that exhibits biochemical and cellular changes similar to those observed in idiopathic PD [96], PEA treatment protected against MPTP-induced neurotoxicity. Namely, PEA reduced microglial and astrocyte activation as well as oxidative stress, protected against alterations in protein dynamics in the substantia nigra, and reversed motor deficits.…”

Section: Parkinson's Disease (Pd)mentioning

confidence: 52%

Effects of Palmitoylethanolamide on Neurodegenerative Diseases: A Review from Rodents to Humans

et al. 2022

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Palmitoylethanolamide (PEA) stands out among endogenous lipid mediators for its neuroprotective, anti-inflammatory, and analgesic functions. PEA belonging to the N-acetylanolamine class of phospholipids was first isolated from soy lecithin, egg yolk, and peanut flour. It is currently used for the treatment of different types of neuropathic pain, such as fibromyalgia, osteoarthritis, carpal tunnel syndrome, and many other conditions. The properties of PEA, especially of its micronized or ultra-micronized forms maximizing bioavailability and efficacy, have sparked a series of innovative research to evaluate its possible application as therapeutic agent for neurodegenerative diseases. Neurodegenerative diseases are widespread throughout the world, and although they are numerous and different, they share common patterns of conditions that result from progressive damage to the brain areas involved in mobility, muscle coordination and strength, mood, and cognition. The present review is aimed at illustrating in vitro and in vivo research, as well as human studies, using PEA treatment, alone or in combination with other compounds, in the presence of neurodegeneration. Namely, attention has been paid to the effects of PEA in counteracting neuroinflammatory conditions and in slowing down the progression of diseases, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, Frontotemporal dementia, Amyotrophic Lateral Sclerosis, and Multiple Sclerosis. Literature research demonstrated the efficacy of PEA in addressing the damage typical of major neurodegenerative diseases.

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Section: Parkinson's Disease (Pd)mentioning

confidence: 52%

Effects of Palmitoylethanolamide on Neurodegenerative Diseases: A Review from Rodents to Humans

et al. 2022

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“…Selective striatal lesions with 6-hydroxydopamine or 3-nitropropionic acid and MPTP caused dystonia in rodents ( 26 , 27 ) and non-human primates ( 6 , 7 , 28 , 29 ). MPTP demonstrates selective preference to injure dopaminergic neurons ( 30 – 32 ). During the dystonic phase in baboons previously treated with IC MPTP, putaminal dopamine D2-like specific binding sites decreased about 30% (measured as soon as 10 days after MPTP) with associated striatal dopamine deficiency of about 97%–98% ( 33 ).…”

Section: Discussionmentioning

confidence: 99%

Transient dystonia correlates with parkinsonism after 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine in non- human primates

Norris¹,

Tian²,

Williams³

et al. 2023

Dystonia

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Unilateral internal carotid artery 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) infusion in non-human primates produces transient contralateral hemi-dystonia followed by stable contralateral hemi-parkinsonism; the relationship between dystonia and parkinsonism remains unclear. We hypothesized that transient dystonia severity following MPTP correlates with parkinsonism severity. In male Macaca nemestrina (n = 3) and M. fascicularis (n = 17) we administered unilateral intra-carotid MPTP, then correlated validated blinded ratings of transient peak dystonia and delayed parkinsonism. We also correlated dystonia severity with post-mortem measures of residual striatal dopamine and nigral neuron counts obtained a mean 53 ± 15 days following MPTP, after resolution of dystonia but during stable parkinsonism. Median latency to dystonia onset was 1 day, and peak severity 2.5 days after MPTP; total dystonia duration was 13.5 days. Parkinsonism peaked a median of 19.5 days after MPTP, remaining nearly constant thereafter. Peak dystonia severity highly correlated with parkinsonism severity (r[18] = 0.82, p < 0.001). Residual cell counts in lesioned nigra correlated linearly with peak dystonia scores (r[18] = −0.68, p=<0.001). Dystonia was not observed in monkeys without striatal dopamine depletion (n = 2); dystonia severity correlated with striatal dopamine depletion when residual nigral cell loss was less than 50% ([11]r = −0.83, p < 0.001) but spanned a broad range with near complete striatal dopamine depletion, when nigral cell loss was greater than 50%. Our data indicate that residual striatal dopamine may not reflect dystonia severity. We speculate on mechanisms of transient dystonia followed by parkinsonism that may be studied using this particular NHP MPTP model to better understand relationships of transient dystonia to nigrostriatal injury and parkinsonism.

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“…When MPTP enters the brain, it is oxidized by the enzyme monoamine oxidase B (MAO-B) within astrocytes and microglia to form 1-methyl-4-phenylpyridinium (MPP + ), which is then released into the extracellular space and subsequently taken up by dopaminergic neurons. Once inside, MPP + is internalized into the mitochondria, where it strongly inhibits complex I of the electron transport chain, leading to cellular degeneration due to decreased energy production capacity [120]. Rotenone [121], another well-known mitochondrial toxin, is also widely used to reproduce the Parkinson's disease phenotype [122][123][124].…”

Section: Pathogenic Impact Of Fatty Acid-binding Proteins On Mitochon...mentioning

confidence: 99%

Pathogenic Impact of Fatty Acid-Binding Proteins in Parkinson’s Disease—Potential Biomarkers and Therapeutic Targets

Kawahata,

Fukunaga

2023

IJMS

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Parkinson’s disease is a neurodegenerative condition characterized by motor dysfunction resulting from the degeneration of dopamine-producing neurons in the midbrain. This dopamine deficiency gives rise to a spectrum of movement-related symptoms, including tremors, rigidity, and bradykinesia. While the precise etiology of Parkinson’s disease remains elusive, genetic mutations, protein aggregation, inflammatory processes, and oxidative stress are believed to contribute to its development. In this context, fatty acid-binding proteins (FABPs) in the central nervous system, FABP3, FABP5, and FABP7, impact α-synuclein aggregation, neurotoxicity, and neuroinflammation. These FABPs accumulate in mitochondria during neurodegeneration, disrupting their membrane potential and homeostasis. In particular, FABP3, abundant in nigrostriatal dopaminergic neurons, is responsible for α-synuclein propagation into neurons and intracellular accumulation, affecting the loss of mesencephalic tyrosine hydroxylase protein, a rate-limiting enzyme of dopamine biosynthesis. This review summarizes the characteristics of FABP family proteins and delves into the pathogenic significance of FABPs in the pathogenesis of Parkinson’s disease. Furthermore, it examines potential novel therapeutic targets and early diagnostic biomarkers for Parkinson’s disease and related neurodegenerative disorders.

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Parkinsonian Syndrome Caused by 1-Methyl-4-Phenyl-1,2,3,6-tetrahydropyridine (MPTP) in Man and Animals

Cited by 5 publications

References 90 publications

Effects of Palmitoylethanolamide on Neurodegenerative Diseases: A Review from Rodents to Humans

Effects of Palmitoylethanolamide on Neurodegenerative Diseases: A Review from Rodents to Humans

Transient dystonia correlates with parkinsonism after 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine in non- human primates

Pathogenic Impact of Fatty Acid-Binding Proteins in Parkinson’s Disease—Potential Biomarkers and Therapeutic Targets

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