Restoration and targeting of aberrant neurotransmitters in Parkinson's disease therapeutics

Yadav, Divya; Kumar, Pravir

doi:10.1016/j.neuint.2022.105327

Cited by 23 publications

(13 citation statements)

References 271 publications

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“…We detected dysregulation in synthesis and metabolism of neuroactive molecules dopamine, glutamate, gamma aminobutyric acid (GABA), and serotonin. Aberrations involving these neurotransmitters in PD is well established 40 . The human gut microbiome has known capacity to not only produce and metabolize these neurotransmitters in the gut, but also to influence their levels in the brain 41 .…”

Section: Functional Inferencementioning

confidence: 99%

Metagenomics of Parkinson’s disease implicates the gut microbiome in multiple disease mechanisms

et al. 2022

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Parkinson’s disease (PD) may start in the gut and spread to the brain. To investigate the role of gut microbiome, we conducted a large-scale study, at high taxonomic resolution, using uniform standardized methods from start to end. We enrolled 490 PD and 234 control individuals, conducted deep shotgun sequencing of fecal DNA, followed by metagenome-wide association studies requiring significance by two methods (ANCOM-BC and MaAsLin2) to declare disease association, network analysis to identify polymicrobial clusters, and functional profiling. Here we show that over 30% of species, genes and pathways tested have altered abundances in PD, depicting a widespread dysbiosis. PD-associated species form polymicrobial clusters that grow or shrink together, and some compete. PD microbiome is disease permissive, evidenced by overabundance of pathogens and immunogenic components, dysregulated neuroactive signaling, preponderance of molecules that induce alpha-synuclein pathology, and over-production of toxicants; with the reduction in anti-inflammatory and neuroprotective factors limiting the capacity to recover. We validate, in human PD, findings that were observed in experimental models; reconcile and resolve human PD microbiome literature; and provide a broad foundation with a wealth of concrete testable hypotheses to discern the role of the gut microbiome in PD.

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Section: Functional Inferencementioning

confidence: 99%

Metagenomics of Parkinson’s disease implicates the gut microbiome in multiple disease mechanisms

et al. 2022

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“…Present data suggests substantial dysregulation in PD microbiome of synthesis and metabolism of small molecules that can modulate neuronal activity, and which are integral to PD pathologies, namely, dopamine, glutamate, gamma aminobutyric acid (GABA), and serotonin. Aberrations involving these neurotransmitters in PD is well-established 43 . The human gut microbiome has known capacity to not only produce and metabolize these neurotransmitters in the gut 44 , but also to influence their levels in the brain 45 .…”

Section: Resultsmentioning

confidence: 99%

Metagenomics of Parkinson’s disease implicates the gut microbiome in multiple disease mechanisms

Wallen

Demirkan

Twa

et al. 2022

Preprint

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Parkinson's disease (PD) may start in the gut and spread to the brain. To investigate the role of gut microbiome, we enrolled 490 PD and 234 control individuals, conducted deep shotgun sequencing of fecal DNA, followed by metagenome-wide association studies requiring significance by two methods (ANCOM-BC and MaAsLin2) to declare disease association. Thirty-percent of species and pathways tested had altered abundances in PD, depicting a widespread dysbiosis. Network analysis showed PD-associated species form polymicrobial clusters that grow or shrink together, and some compete. Metagenomic profile of PD indicates a disease permissive microbiome, evidenced by overabundance of pathogens and immunogenic components, dysregulated neuroactive signaling, preponderance of molecules that induce alpha-synuclein pathology, and over-production of toxicants; with the reduction in anti-inflammatory and neuroprotective factors limiting the capacity to recover. These data provide a broad foundation with a wealth of concrete testable hypotheses to discern the role of the gut microbiome in PD.

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“…As PD progresses, alpha-synuclein accumulation spreads from the dopaminergic system in the midbrain to the cortex, resulting in changes that manifest as cognitive and sensory symptoms in addition to motor symptoms 5 , 48 . BR has been reported to correlate positively with dopaminergic neuron activation 22 .…”

Section: Discussionmentioning

confidence: 99%

Prevalence and characteristics of dry eye disease in Parkinson’s disease: a systematic review and meta-analysis

Nagino

Sung

Oyama

et al. 2022

Sci Rep

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We investigated and characterized the prevalence of dry eye disease (DED) in Parkinson’s disease (PD). PubMed and EMBASE databases were searched for relevant studies between January 1, 1979 and March 10, 2022. Quality was assessed using the Joanna Briggs Institute Critical Appraisal Checklist. Study-specific estimates were combined using the DerSimonian–Laird random-effects model. Prevalence of subjective DED symptoms in patients with PD and mean differences in blink rate, corneal thickness, tear film breakup time, and tear secretion volume on Schirmer test I were compared to those in controls. Of 383 studies, 13 (1519 patients with PD) and 12 were included in qualitative and quantitative syntheses, respectively. Meta-analysis revealed a 61.1% prevalence of subjective DED symptoms in PD and that, compared with controls, patients with PD had significantly lower blink rate, thinner corneal thickness, shorter tear film breakup time, and lower tear secretion volumes on Schirmer test I, without and with anesthesia.

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Restoration and targeting of aberrant neurotransmitters in Parkinson's disease therapeutics

Cited by 23 publications

References 271 publications

Metagenomics of Parkinson’s disease implicates the gut microbiome in multiple disease mechanisms

Metagenomics of Parkinson’s disease implicates the gut microbiome in multiple disease mechanisms

Metagenomics of Parkinson’s disease implicates the gut microbiome in multiple disease mechanisms

Prevalence and characteristics of dry eye disease in Parkinson’s disease: a systematic review and meta-analysis

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