2016

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! ! Rethinking Parkinson's disease: could dopamine reduction therapy have clinical utility? | Journal of Neurology
! ! Rethinking Parkinson's disease: could dopamine reduction therapy have clinical utility? | Journal of Neurology
Following reports of low striatal dopamine content in Parkinson’s disease, levodopa was shown to rapidly reverse hypokinesis, establishing the model of disease as one of dopamine deficiency. Dopaminergic therapy became standard of care, yet it failed to reverse the disease, suggesting the understanding of disease was incomplete. The literature suggests the potential for toxicity of dopamine and its metabolites, perhaps more relevant given the recent evidence for elevated cytosolic dopamine levels in the dopaminergic neurons of people with Parkinson’s. To understand the relevance of these data, multiple investigations are reviewed that tested dopamine reduction therapy as an alternative to dopaminergic agents. The data from use of an inhibitor of dopamine synthesis in experimental models suggest that such an approach could reverse disease pathology, which suggests that cytosolic dopamine excess is a primary driver of disease. These data support clinical investigation of dopamine reduction therapy for Parkinson’s disease. Doing so will determine whether these experimental models are predictive and this treatment strategy is worth pursuing further. If clinical data are positive, it could warrant reconsideration of our disease model and treatment strategies, including a shift from dopaminergic to dopamine reduction treatment of the disease.
·link.springer.com·
! ! Rethinking Parkinson's disease: could dopamine reduction therapy have clinical utility? | Journal of Neurology
! ! Right Brain Bio
! ! Right Brain Bio
Right Brain Bio is developing a data-driven treatment for Parkinson's - one so revolutionary that it will transform disease understanding and treatment.
·rightbrainbio.com·
! ! Right Brain Bio
A neuroprotective dose of trehalose is harmless to metabolic organs: comprehensive histopathological analysis of liver, pancreas, and kidney - PubMed
A neuroprotective dose of trehalose is harmless to metabolic organs: comprehensive histopathological analysis of liver, pancreas, and kidney - PubMed
Our study demonstrates that systemic trehalose administration preserved the typical histological architecture of the organs involved in its metabolism, supporting its safety as a potential neuroprotective agent.
·pubmed.ncbi.nlm.nih.gov·
A neuroprotective dose of trehalose is harmless to metabolic organs: comprehensive histopathological analysis of liver, pancreas, and kidney - PubMed
Association between increased and decreased gut microbiota abundance and Parkinson's disease: A systematic review and subgroup meta-analysis - PubMed
Association between increased and decreased gut microbiota abundance and Parkinson's disease: A systematic review and subgroup meta-analysis - PubMed
Patients in the PD cohort exhibited distinctive microbiota compositions compared to healthy individuals, with unique differential patterns in gut microbiome abundance at the phylum, family, and genus levels that may be associated wtih PD pathogenesis.
·pubmed.ncbi.nlm.nih.gov·
Association between increased and decreased gut microbiota abundance and Parkinson's disease: A systematic review and subgroup meta-analysis - PubMed
Gut brain axis: an insight into microbiota role in Parkinson's disease - PubMed
Gut brain axis: an insight into microbiota role in Parkinson's disease - PubMed
Parkinson's disease (PD) is one of the most common progressive neurodegenerative diseases. It is characterized neuropathologically by the presence of alpha-synuclein containing Lewy Bodies in the substantia nigra of the brain with loss of dopaminergic neurons in the pars compacta of the substantia n …
·pubmed.ncbi.nlm.nih.gov·
Gut brain axis: an insight into microbiota role in Parkinson's disease - PubMed
Gut Microbial Metabolites in Parkinson's Disease: Implications of Mitochondrial Dysfunction in the Pathogenesis and Treatment - PubMed
Gut Microbial Metabolites in Parkinson's Disease: Implications of Mitochondrial Dysfunction in the Pathogenesis and Treatment - PubMed
The search for therapeutic targets for Parkinson's disease (PD) is hindered by the incomplete understanding of the pathophysiology of the disease. Mitochondrial dysfunction is an area with high potential. The neurobiological signaling connections between the gut microbiome and the central nervous sy …
·pubmed.ncbi.nlm.nih.gov·
Gut Microbial Metabolites in Parkinson's Disease: Implications of Mitochondrial Dysfunction in the Pathogenesis and Treatment - PubMed
Literature review and meta-analysis of environmental toxins associated with increased risk of Parkinson's disease - PubMed
Literature review and meta-analysis of environmental toxins associated with increased risk of Parkinson's disease - PubMed
Parkinson's disease (PD) is a neurodegenerative disorder and leading cause of death worldwide, whose pathogenesis has been linked to toxic environmental exposures. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (i) to compile, and group by exposure …
·pubmed.ncbi.nlm.nih.gov·
Literature review and meta-analysis of environmental toxins associated with increased risk of Parkinson's disease - PubMed
Mitochondrial Dysfunction in Genetic and Non-Genetic Parkinson's Disease - PubMed
Mitochondrial Dysfunction in Genetic and Non-Genetic Parkinson's Disease - PubMed
Mitochondrial dysfunction is a hallmark of Parkinson's disease (PD) pathogenesis, contributing to increased oxidative stress and impaired endo-lysosomal-proteasome system efficiency underlying neuronal injury. Genetic studies have identified 19 monogenic mutations-accounting for ~10% of PD cases-tha …
·pubmed.ncbi.nlm.nih.gov·
Mitochondrial Dysfunction in Genetic and Non-Genetic Parkinson's Disease - PubMed
Oral Trehalose Intake Modulates the Microbiota-Gut-Brain Axis and Is Neuroprotective in a Synucleinopathy Mouse Model - PubMed
Oral Trehalose Intake Modulates the Microbiota-Gut-Brain Axis and Is Neuroprotective in a Synucleinopathy Mouse Model - PubMed
Parkinson's disease (PD) is a neurodegenerative disease affecting dopaminergic neurons in the nigrostriatal and gastrointestinal tracts, causing both motor and non-motor symptoms. This study examined the neuroprotective effects of trehalose. This sugar is confined in the gut due to the absence of tr …
·pubmed.ncbi.nlm.nih.gov·
Oral Trehalose Intake Modulates the Microbiota-Gut-Brain Axis and Is Neuroprotective in a Synucleinopathy Mouse Model - PubMed
The History Of Chlorine Dioxide - by Pierre Kory, MD, MPA
The History Of Chlorine Dioxide - by Pierre Kory, MD, MPA
Chlorine dioxide was discovered over 200 years ago. It's use has steadily expanded into many industries and therapeutic applications despite a near global regulatory blockade on clinical research.
·pierrekorymedicalmusings.com·
The History Of Chlorine Dioxide - by Pierre Kory, MD, MPA
The role of amphipathic and cationic helical peptides in Parkinson's disease - PubMed
The role of amphipathic and cationic helical peptides in Parkinson's disease - PubMed
Peptides are attracting a growing interest for therapeutic applications in biomedicine. In Parkinson's disease (PD), different human endogenous peptides have been associated with beneficial effects, including protein aggregation inhibition, reduced inflammation, or the protection of dopaminergic neu …
·pubmed.ncbi.nlm.nih.gov·
The role of amphipathic and cationic helical peptides in Parkinson's disease - PubMed
Use of medium chain triglyceride (MCT) oil in subjects with Alzheimer's disease: A randomized, double‐blind, placebo‐controlled, crossover study, with an open‐label extension - PMC
Use of medium chain triglyceride (MCT) oil in subjects with Alzheimer's disease: A randomized, double‐blind, placebo‐controlled, crossover study, with an open‐label extension - PMC
Cerebral glucose and insulin metabolism is impaired in Alzheimer's disease (AD). Ketones provide alternative energy. Will medium chain triglyceride (MCT) oil, a nutritional source of ketones, impact cognition in AD? This was a 6‐month randomized, ...
·pmc.ncbi.nlm.nih.gov·
Use of medium chain triglyceride (MCT) oil in subjects with Alzheimer's disease: A randomized, double‐blind, placebo‐controlled, crossover study, with an open‐label extension - PMC
Aging-Associated Amyloid-β Plaques and Neuroinflammation in Bottlenose Dolphins (Tursiops truncatus) and Novel Cognitive Health-Supporting Roles of Pentadecanoic Acid (C15:0)
Aging-Associated Amyloid-β Plaques and Neuroinflammation in Bottlenose Dolphins (Tursiops truncatus) and Novel Cognitive Health-Supporting Roles of Pentadecanoic Acid (C15:0)
There is an urgent need to identify interventions that broadly target aging-related cognitive decline and progression to Alzheimer’s disease (AD). Bottlenose dolphins (Tursiops truncatus) have histologic changes similar to AD in humans, and they also develop shared age-associated co-morbidities identified as risk factors for AD in humans, including type 2 diabetes, ferroptosis, and iron overload, which can be driven by nutritional C15:0 deficiency. We hypothesized that (1) dolphins would have amyloid beta (Aβ) plaques and neuroinflammation that paralleled that of humans in relation to age-related progression, quantitative concentration, and brain region; and (2) C15:0 would have dose-dependent activities relevant to protecting cognitive health. Quantitative immunohistochemistry staining was used to assess 68 tissues from archived brains of 19 Navy dolphins to evaluate associations among amyloid beta (Aβ) plaques and neuroinflammation by brain region, sex, and age group. Further, dose-dependent C15:0 activities, using a third-party panel intended to screen for potential AD therapeutics, were evaluated. Similar to humans, dolphins had the highest Aβ plaque density variation in the hippocampus (90th percentile of 4.95 plaques/mm2), where plaque density increased with age (p = 0.05). All measured markers of neuroinflammation were detected, including the highest concentrations of activated microglia (CD68+) in the hippocampus (0.46 ± 0.38 cells/mm2). C15:0 was a dose-dependent inhibitor of two targets, fatty acid amide hydrolase (FAAH) (IC50 2.5 µM, 89% maximum inhibition at 50 µM relative to URB597) and monoamine oxidase B (MAO-B) (IC50 19.4 µM, 70% maximum inhibition at 50 µM relative to R(-)-Deprenyl). These activities have demonstrated efficacy against Aβ formation and neuroinflammation, including protection of cognitive function in the hippocampus. These findings suggest that, in addition to protecting against AD co-morbidities, C15:0 may play a distinct role in supporting cognitive health, especially at higher concentrations.
·mdpi.com·
Aging-Associated Amyloid-β Plaques and Neuroinflammation in Bottlenose Dolphins (Tursiops truncatus) and Novel Cognitive Health-Supporting Roles of Pentadecanoic Acid (C15:0)