Potential New Insights Into the Molecular Mechanisms of Methamphetamine-Induced Neurodegeneration

Wrona, Monika Z.; Yang, Zhifei; Zhang, Fa; Dryhurst, Glenn

doi:10.1037/e495572006-011

Cited by 32 publications

(37 citation statements)

References 75 publications

(122 reference statements)

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“…Experimental evidence suggests that in Alzheimer's disease and disorders of copper storage, serotonin oxidation produces 4,5-dihydroxytryptamine which further oxidizes to compounds that inhibit acetylcholine esterase and cause oxidative stress [189][190][191][192]. Furthermore, the production of neurotoxic oxidation products of cytosolic serotonin has been proposed as a possible mechanism of methamphetamine neurotoxicity in these neurons [187,191,193].…”

Section: Vesicular Transport and Neurotransmitter Toxicitymentioning

confidence: 98%

Protective Actions of the Vesicular Monoamine Transporter 2 (VMAT2) in Monoaminergic Neurons

2009

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Vesicular monoamine transporters (VMATs) are responsible for the packaging of neurotransmitters such as dopamine, serotonin, norepinephrine, and epinephrine into synaptic vesicles. These proteins evolved from precursors in the major facilitator superfamily of transporters and are among the members of the toxin extruding antiporter family. While the primary function of VMATs is to sequester neurotransmitters within vesicles, they can also translocate toxicants away from cytosolic sites of action. In the case of dopamine, this dual role of VMAT2 is combined-dopamine is more readily oxidized in the cytosol where it can cause oxidative stress so packaging into vesicles serves two purposes: neurotransmission and neuroprotection. Furthermore, the deleterious effects of exogenous toxicants on dopamine neurons, such as MPTP, can be attenuated by VMAT2 activity. The active metabolite of MPTP can be kept within vesicles and prevented from disrupting mitochondrial function thereby sparing the dopamine neuron. The highly addictive drug methamphetamine is also neurotoxic to dopamine neurons by using dopamine itself to destroy the axon terminals. Methamphetamine interferes with vesicular sequestration and increases the production of dopamine, escalating the amount in the cytosol and leading to oxidative damage of terminal components. Vesicular transport seems to resist this process by sequestering much of the excess dopamine, which is illustrated by the enhanced methamphetamine neurotoxicity in VMAT2-deficient mice. It is increasingly evident that VMAT2 provides neuroprotection from both endogenous and exogenous toxicants and that while VMAT2 has been adapted by eukaryotes for synaptic transmission, it is derived from phylogenetically ancient proteins that originally evolved for the purpose of cellular protection.

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Section: Vesicular Transport and Neurotransmitter Toxicitymentioning

confidence: 98%

Protective Actions of the Vesicular Monoamine Transporter 2 (VMAT2) in Monoaminergic Neurons

2009

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“…Furthermore, to reiterate from Section 4.1.1., the increased accumulation of ROS may act as a signal for the initiation of pro-apoptotic cascades (Oh and Lim, 2005) that has been demonstrated in the literature on Tat alone (Kruman et al, 1998), and in the literature on COC administration Fosnaugh et al, 1995). Furthermore, D1 receptors facilitate the release of DA, and DA has been shown to auto-oxidize (Flora et al, 2003;Wrona et al, 1997) to form ROS and reactive quinones. Thus, it is reasonable to expect consistently higher levels of oxidation in the Tat+COC exposed tissue.…”

Section: Hiv + Psychostimulant Mechanisms-mentioning

confidence: 99%

Neurotoxic profiles of HIV, psychostimulant drugs of abuse, and their concerted effect on the brain: Current status of dopamine system vulnerability in NeuroAIDS

Ferris

Mactutus

Booze

2008

Neuroscience & Biobehavioral Reviews

118

131

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There are roughly 30 to 40 million HIV infected individuals in the world as of December 2007, and drug abuse directly contributes to one-third of all HIV-infections in the United States. Antiretroviral therapy has increased the lifespan of HIV-seropositives, but CNS function often remains diminished, effectively decreasing quality of life. A modest proportion may develop HIV-associated dementia, the severity and progression of which is increased with drug abuse. HIV and drugs of abuse in the CNS target subcortical brain structures and DA systems in particular. This toxicity is mediated by a number of neurotoxic mechanisms, including but not limited to, aberrant immune response and oxidative stress. Therefore, novel therapeutic strategies must be developed that can address a wide variety of disparate neurotoxic mechanisms and apoptotic cascades. This paper reviews the research pertaining to the where, what, and how of HIV and cocaine/methamphetamine toxicity in the CNS. Specifically, where these toxins most affect the brain, what aspects of the virus are neurotoxic, and how these toxins mediate neurotoxicity.

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“…Finally, we examined the effects of TNF-␣ on [ 3 H]DA uptake into synaptic vesicle preparations, because redistribution of DA from synaptic vesicles to cytoplasmic compartments through interaction with VMAT-2, and consequent elevation of oxidizable DA concentrations, has been postulated to be primarily responsible for DA terminal injury by METH and amphetamines (Cubellus et al, 1994;Liu and Edwards, 1997;Wrona et al, 1997;Uhl, 1998). As shown in Figure 6 D, TNF-␣ (4 g, i.p.)…”

Section: Effects Of Tnf-␣ On Meth-induced Da Responsesmentioning

confidence: 99%

Role of Tumor Necrosis Factor-α in Methamphetamine-Induced Drug Dependence and Neurotoxicity

Nakajima¹,

Yamada²,

Nagai³

et al. 2004

J. Neurosci.

162

155

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Potential New Insights Into the Molecular Mechanisms of Methamphetamine-Induced Neurodegeneration

Cited by 32 publications

References 75 publications

Protective Actions of the Vesicular Monoamine Transporter 2 (VMAT2) in Monoaminergic Neurons

Protective Actions of the Vesicular Monoamine Transporter 2 (VMAT2) in Monoaminergic Neurons

Neurotoxic profiles of HIV, psychostimulant drugs of abuse, and their concerted effect on the brain: Current status of dopamine system vulnerability in NeuroAIDS

Role of Tumor Necrosis Factor-α in Methamphetamine-Induced Drug Dependence and Neurotoxicity

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