Metabotropic Glutamate Receptors for Parkinson's Disease Therapy

Gasparini, F.; Paolo, Thérèse Di; Gomez‐Mancilla, Baltazar

doi:10.1155/2013/196028

Cited by 37 publications

(41 citation statements)

References 120 publications

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“…Glutamate concentration was raised in ALS patients, and glutamate inhibitors (for example, riluzole) were presented as an alternative cure for ALS patients (Sako et al, 2016). In addition, aberrant glutamate signaling in the basal ganglia may be involved in PD development (Gasparini et al, 2013). Glycine behaves as a neurotransmitter (López-Corcuera et al, 2001), and phenylalanine have a significant role in neurotransmitter regulation (Humphries et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Metabolic Biomarkers and Neurodegeneration: A Pathway Enrichment Analysis of Alzheimer's Disease, Parkinson's Disease, and Amyotrophic Lateral Sclerosis

Kori

Aydın

Unal

et al. 2016

OMICS: A Journal of Integrative Biology

125

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Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) lack robust diagnostics and prognostic biomarkers. Metabolomics is a postgenomics field that offers fresh insights for biomarkers of common complex as well as rare diseases. Using data on metabolite-disease associations published in the previous decade (2006-2016) in PubMed, ScienceDirect, Scopus, and Web of Science, we identified 101 metabolites as putative biomarkers for these three neurodegenerative diseases. Notably, uric acid, choline, creatine, L-glutamine, alanine, creatinine, and N-acetyl-L-aspartate were the shared metabolite signatures among the three diseases. The disease-metabolite-pathway associations pointed out the importance of membrane transport (through ATP binding cassette transporters), particularly of arginine and proline amino acids in all three neurodegenerative diseases. When disease-specific and common metabolic pathways were queried by using the pathway enrichment analyses, we found that alanine, aspartate, glutamate, and purine metabolism might act as alternative pathways to overcome inadequate glucose supply and energy crisis in neurodegeneration. These observations underscore the importance of metabolite-based biomarker research in deciphering the elusive pathophysiology of neurodegenerative diseases. Future research investments in metabolomics of complex diseases might provide new insights on AD, PD, and ALS that continue to place a significant burden on global health.

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Section: Discussionmentioning

confidence: 99%

Metabolic Biomarkers and Neurodegeneration: A Pathway Enrichment Analysis of Alzheimer's Disease, Parkinson's Disease, and Amyotrophic Lateral Sclerosis

Kori

Aydın

Unal

et al. 2016

OMICS: A Journal of Integrative Biology

125

View full text Add to dashboard Cite

show abstract

“…A third strategy that has led to specific targets for therapeutic trials has come from studies of drugs that suppress levodopa-induced dyskinesias in Parkinson's disease or its animal models. Dyskinesias sometimes have a dystonic quality, and negative allosteric modulators of metabotropic glutamate receptor mGluR5 appear to specifically suppress dystonic dyskinesias in animal models [25,26]. These observations raise the intriguing possibility that this category of drugs may suppress dystonia in other disorders, but further studies are needed.…”

Section: Potential Sources Of Novel Dystonia Drugsmentioning

confidence: 99%

Designing Clinical Trials for Dystonia

et al. 2014

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With advances in the understanding of the pathophysiology of dystonia, novel therapeutics are being developed. Such therapies will require clinical investigation ranging from exploratory studies to examine safety, tolerability, dosage selection, and preliminary efficacy to confirmatory studies to evaluate efficacy definitively. As dystonia is a rare and complex disorder with clinical and etiological heterogeneity, clinical trials will require careful consideration of the trial design, including enrollment criteria, concomitant medication use, and outcome measures. Given the complexities of designing and implementing efficient clinical trials, it is important for clinicians and statisticians to collaborate closely throughout the clinical development process and that each has a basic understanding of both the clinical and statistical issues that must be addressed. To facilitate designing appropriate clinical trials in this field, we review important general clinical trial and regulatory principles, and discuss the critical components of trials with an emphasis on considerations specific to dystonia. Additionally, we discuss designs used in early exploratory, late exploratory, and confirmatory phases, including adaptive designs.

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“…Patterns of neuronal discharge within the basal ganglia are disturbed in PD [204]. The loss of DA in the SNpc increases the overall excitatory drive in the BG, disrupting voluntary motor control and causing the characteristic features of PD [205].…”

Section: Structural Alteration In Pdmentioning

confidence: 99%

Restoration of Mitochondrial Dysfunction in 6-Hydroxydopamine Induced Parkinson’s disease: a Complete Review

Mehan¹,

Kaur²,

Dudi³

et al. 2017

Open J Parkinsons Dis Treatm

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Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by neuronal cell death in the specifi c brain region like basal ganglia, cerebral cortex and hippocampus. Symptoms associated with PD patients are rigidity, akathesia, tremor, postural imbalance, cognitive and memory dysfunctions. Pathological hallmarks are dopaminergic neuronal degeneration, neuro-infl ammation, oxidative stress, free radical generation. In the typical Parkinson's disease model, 6-Hydroxydopamine (6-OHDA) is delivered unilaterally by stereotactic injection into the SNc (substantia nigra pars-compacta) or the striatum mimics the PD symptoms. In addition, it has been shown that 6-OHDA is toxic to complex I & IV of the mitochondrial respiratory chain, leading to subsequent respiratory inhibition and further processed ATP depletion, oxidative stress and neuro-infl ammation. Forskolin (FSK), a diterpene natural plant phytochemical obtained from (Coleus Forskohli), a potent direct activator of adenyl cyclase (AC) enzyme which further activates cAMP/PK A /CREB pathway. FSK mediated activation of AC/cAMP/PK A / CREB pathway is responsible for various neuroprotective mechanisms Based on important and versatile role of FSK, the present study has been designed to investigate the role of cAMP mediated CREB activation in 6-hydroxydopamine induced mitochondrial associated neurotoxicity in rats. Further the studies are extended to understand the disease pathogenesis and to investigate and discuss the various possible central mechanisms involved in the effect of such targets using behavioral paradigm and biochemical markers of neurodegeneration.

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Metabotropic Glutamate Receptors for Parkinson's Disease Therapy

Cited by 37 publications

References 120 publications

Metabolic Biomarkers and Neurodegeneration: A Pathway Enrichment Analysis of Alzheimer's Disease, Parkinson's Disease, and Amyotrophic Lateral Sclerosis

Metabolic Biomarkers and Neurodegeneration: A Pathway Enrichment Analysis of Alzheimer's Disease, Parkinson's Disease, and Amyotrophic Lateral Sclerosis

Designing Clinical Trials for Dystonia

Restoration of Mitochondrial Dysfunction in 6-Hydroxydopamine Induced Parkinson’s disease: a Complete Review

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