Thiamine and Parkinson's disease

Lương, Khanh vinh quốc; Nguyễn, Lan

doi:10.1016/j.jns.2012.02.008

Cited by 41 publications

(17 citation statements)

References 149 publications

(150 reference statements)

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“…Thiamine deficiency (TD) may occur in numerous conditions such as cancer and diabetes, or following bariatric surgery [ 1 ]. Additionally, it may occur in neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease, although it is most prevalent in chronic alcoholics [ 2 – 5 ]. Wernicke-Korsakoff Syndrome (WKS) is a life-threatening consequence of TD occurring in up to 12.5% of chronic alcoholics [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Thiamine deficiency activates hypoxia inducible factor-1α to facilitate pro-apoptotic responses in mouse primary astrocytes

Zera

Zastre

2017

PLoS ONE

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Thiamine is an essential enzyme cofactor required for proper metabolic function and maintenance of metabolism and energy production in the brain. In developed countries, thiamine deficiency (TD) is most often manifested following chronic alcohol consumption leading to impaired mitochondrial function, oxidative stress, inflammation and excitotoxicity. These biochemical lesions result in apoptotic cell death in both neurons and astrocytes. Comparable histological injuries in patients with hypoxia/ischemia and TD have been described in the thalamus and mammillary bodies, suggesting a congruency between the cellular responses to these stresses. Consistent with hypoxia/ischemia, TD stabilizes and activates Hypoxia Inducible Factor-1α (HIF-1α) under physiological oxygen levels. However, the role of TD-induced HIF-1α in neurological injury is currently unknown. Using Western blot analysis and RT-PCR, we have demonstrated that TD induces HIF-1α expression and activity in primary mouse astrocytes. We observed a time-dependent increase in mRNA and protein expression of the pro-apoptotic and pro-inflammatory HIF-1α target genes MCP1, BNIP3, Nix and Noxa during TD. We also observed apoptotic cell death in TD as demonstrated by PI/Annexin V staining, TUNEL assay, and Cell Death ELISA. Pharmacological inhibition of HIF-1α activity using YC1 and thiamine repletion both reduced expression of pro-apoptotic HIF-1α target genes and apoptotic cell death in TD. These results demonstrate that induction of HIF-1α mediated transcriptional up-regulation of pro-apoptotic/inflammatory signaling contributes to astrocyte cell death during thiamine deficiency.

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Section: Introductionmentioning

confidence: 99%

Thiamine deficiency activates hypoxia inducible factor-1α to facilitate pro-apoptotic responses in mouse primary astrocytes

Zera

Zastre

2017

PLoS ONE

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“…Thiamin (also known as vitamin B1) is widely used in neuropharmacology. In particular, its administration causes a transient improvement in cognitive function of some patients affected by neurodegenerative diseases, including Alzheimer’s disease (AD) and Parkinson’s disease (PD) 1 2 3 4 5 . The importance of thiamin administration in elderly is supported by the fact that the levels of thiamin and its coenzyme form, thiamin diphosphate (ThDP), are decreased with age 6 .…”

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confidence: 99%

Molecular mechanisms of the non-coenzyme action of thiamin in brain: biochemical, structural and pathway analysis

Mkrtchyan

Aleshin

Parkhomenko

et al. 2015

Sci Rep

114

124

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Thiamin (vitamin B1) is a pharmacological agent boosting central metabolism through the action of the coenzyme thiamin diphosphate (ThDP). However, positive effects, including improved cognition, of high thiamin doses in neurodegeneration may be observed without increased ThDP or ThDP-dependent enzymes in brain. Here, we determine protein partners and metabolic pathways where thiamin acts beyond its coenzyme role. Malate dehydrogenase, glutamate dehydrogenase and pyridoxal kinase were identified as abundant proteins binding to thiamin- or thiazolium-modified sorbents. Kinetic studies, supported by structural analysis, revealed allosteric regulation of these proteins by thiamin and/or its derivatives. Thiamin triphosphate and adenylated thiamin triphosphate activate glutamate dehydrogenase. Thiamin and ThDP regulate malate dehydrogenase isoforms and pyridoxal kinase. Thiamin regulation of enzymes related to malate-aspartate shuttle may impact on malate/citrate exchange, responsible for exporting acetyl residues from mitochondria. Indeed, bioinformatic analyses found an association between thiamin- and thiazolium-binding proteins and the term acetylation. Our interdisciplinary study shows that thiamin is not only a coenzyme for acetyl-CoA production, but also an allosteric regulator of acetyl-CoA metabolism including regulatory acetylation of proteins and acetylcholine biosynthesis. Moreover, thiamin action in neurodegeneration may also involve neurodegeneration-related 14-3-3, DJ-1 and β-amyloid precursor proteins identified among the thiamin- and/or thiazolium-binding proteins.

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“…. In a previous publication, we identified a number of proteins that link thiamine to PD pathology . In the present paper, we will further discuss the relationship between thiamine and PD.…”

Section: Introductionmentioning

confidence: 85%

“…In addition, the intestinal absorption of thiamine is sufficient in young people but may be reduced with age . Parental administration of thiamine may be suitable for patients with PD . Thus, further studies are needed to determine the potential benefits of using thiamine as a treatment for PD.…”

Section: Discussionmentioning

confidence: 99%

The Beneficial Role of Thiamine in Parkinson Disease

Lương

Nguyễn

2013

CNS Neurosci Ther

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Parkinson disease (PD) is the second most common form of neurodegeneration among elderly individuals. PD is clinically characterized by tremors, rigidity, slowness of movement, and postural imbalance. In this paper, we review the evidence for an association between PD and thiamine. Interestingly, a significant association has been demonstrated between PD and low levels of serum thiamine, and thiamine supplements appear to have beneficial clinical effects against PD. Multiple studies have evaluated the connection between thiamine and PD pathology, and candidate pathways involve the transcription factor Sp1, p53, Bcl-2, caspase-3, tyrosine hydroxylase, glycogen synthase kinase-3β, vascular endothelial growth factor, advanced glycation end products, nuclear factor kappa B, mitogen-activated protein kinase, and the reduced form of nicotinamide adenine dinucleotide phosphate. Thus, a review of the literature suggests that thiamine plays a role in PD, although further investigation into the effects of thiamine in PD is needed.

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Thiamine and Parkinson's disease

Cited by 41 publications

References 149 publications

Thiamine deficiency activates hypoxia inducible factor-1α to facilitate pro-apoptotic responses in mouse primary astrocytes

Thiamine deficiency activates hypoxia inducible factor-1α to facilitate pro-apoptotic responses in mouse primary astrocytes

Molecular mechanisms of the non-coenzyme action of thiamin in brain: biochemical, structural and pathway analysis

The Beneficial Role of Thiamine in Parkinson Disease

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