Alpha-synuclein {90000275}

Shared Reference Notes

• [1.1] 
  - #Beta-glucan food supplement > significant decrease in the Childhood #Autism Rating Scale score in all of the children of the Nichi Glucan Gr.2 compared with the control. Plasma levels of alpha-synuclein were significantly higher in (Nichi Glucan) than in the control group.
• [1.2] [#Autism] [#Amyloid, #Beta-glucan, #Curli] [#Nichi Glucan] 
• [1.3] [#Parkinson’s Disease] 
  - a positive correlation between intestinal inflammation and expression of α-syn and observed α-syn to exhibit immune-modulatory or chemo-attractive properties that induce migration of neutrophils and monocytes and stimulate dendritic cells maturation. - dysbiosis and exposure to bacterial endotoxin possibly initiate α-syn misfolding by prompting GI inflammation and hyperpermeability in PD patients. - exposure to bacteria-producing amyloid protein curli can induce α-syn accumulation in the gut and brain of mice
• [1.4] 
  - a decrease of pH resulted in more than threefold increase in the α-Syn dimers lifetimes with some variability between the α-Syn species.
• [1.5] [#Parkinson’s Disease] 
• [1.6] [#Parkinson’s Disease] 
  - #Curli, an amyloidogenic protein produced by Gram-negative Escherichia coli, induces alpha-synuclein aggregation and accelerates disease in the gut and neurodegeneration in the brain. - Many Enterobacteriaceae species encode #Curli.
• [#Parkinson’s Disease] - alpha-synuclein fibrils injected into gut induce alpha-synuclein pathology which spreads from gut to brain, and that #Vagotomy stops the spread. - persons who had complete truncal #Vagotomy decades earlier had substantially reduced incidence of PD later in life
• [1.7] [#Covid-19, #Parkinson’s Disease] 
  - overexpression of α-synuclein in PD patients may limit SARS-CoV-2 neuroinvasion and degeneration of dopaminergic neurons; however, on the other hand, this virus can speed up the α-synuclein aggregation.
• [1.8] 
  - #Butyrate induces the breakdown of α-synuclein and enhances remyelination in mice cerebellar slice cultures
• [1.9] [#Parkinson’s Disease] 
• [#Hydrogen sulfide] - gut inflammation reduces the capacity of H2S inactivation system, which allows #Desulfovibrio -produced H2S to accumulate and enhance alpha-syn aggregation.
• [#Lipopolysaccharide] - lipopolysaccharides which are known to be present in the outer membrane of Gram-negative bacteria, including #Desulfovibrio bacteria, may be an additional virulence factor. Lipopolysaccharides have been shown to modulate alpha-syn aggregation
• [#Parkinson’s Disease] [#Hydrogen sulfide] - H2S has been reported to facilitate the release of cytochrome c from mitochondria to the cytoplasm in human cells. - cytochrome c potentially triggers alpha-syn aggregation in the presence of reactive oxygen species
• [#Parkinson’s Disease] [#Escherichia coli] - #Desulfovibrio strains, particularly those from PD patients, were more competent than #Curli-producing E. coli in stimulating the accumulation of larger and more abundant alpha-syn aggregates.
• [1.11] 
  - #Desulfovibrio is a #Hydrogen sulfide (H2S) and #Lipopolysaccharide (LPS)-producing bacteria. - LPS-treated mice would present intestinal hyperpermeability and a higher level of pathological α-syn accumulation
• [#Parkinson’s Disease] [#Hydrogen sulfide] - The production of H2S also had a potential of inducing α-syn oligomerization, an initial step of α-synucleinopathy, and inhibiting gastrointestinal motility.
• [1.12] [#Parkinson’s Disease] 
  - CD4+ T cells that respond prominently to two regions of the α-syn protein are found in the blood of PD patients. - the immune response to the α-syn32-46 region is restricted to patients carrying a specific HLA haplotype. - α-syn32-46 immunizations in mice in which their native MHCII allele was substituted by the human HLA-DRB1∗15:01 allele recapitulate multiple aspects of the immune response seen in PD patients. - These include loss of ENS neurons, a progressive decrease in dopaminergic neuronal processes in the ENS, transient weight loss, and constipation, reminiscent of gastroenterological deficits reported in PD patients 20 years prior to disease onse
• [1.13] [#Parkinson’s Disease] [#Akkermansia muciniphila] 
  - A. muciniphila (typical strain) induced mitochondrial calcium overload and α-synuclein aggregation in an enteroendocrine cell line
• [#Parkinson’s Disease] - The deposition of α-synuclein is not only found in the gastrointestinal tract of PD patients with gastrointestinal symptoms but also in the gastrointestinal tract of patients before they present with PD-related motor symptoms. - This indicated that α-synuclein pathology is likely initiated in the ENS first, and then spreads to the CNS via the vagus nerve
• [#Parkinson’s Disease] - The increases of #Deoxycholic acid and #Lithocholic acid can propel the accumulation of pathological α-synuclein aggregates, which can potentially propagate from the gut to the brain through retrograde transport
• [#Parkinson’s Disease] - #Ursodeoxycholic acid is another secondary bile acid that has neuroprotective effects an can prevent the damaging effects of #Deoxycholic acid and #Lithocholic acid. - In a chronic PD mouse model, pretreatment with tauroursodeoxycholic acid can protect against dopaminergic neuronal damage, prevent microglial and astroglial activation, as well as the dopamine and 3-4-dihydroxyphenulacetic acid reductions caused by MPTP. - Pretreatment with tauroursodeoxycholic acid can prevent protein oxidation and autophagy, in addition to inhibiting α-synuclein aggregation
• [#Parkinson’s Disease] - oral administration of #Proteus mirabilis, increased markedly in PD mouse models, was sufficient to provoke selective death of #Dopamine neurons and motor deficits in mice, accompanied by neuroinflammation and accumulation of aggregates of α-synuclein in both the colon and brain
• [1.14] [#Parkinson’s Disease] 
  - PD > abnormal αSyn can spread in a prion-like manner via the vagus nerve to the brain.
• [#Parkinson’s Disease] - Either gavaged or supplemented in a human fecal microbiota transplant, #Curli promotes PD pathologies, such as αSyn aggregation, in gut and brain.
• [#Parkinson’s Disease] - Alpha-synuclein overexpression in isolated microglia and peripheral monocytes greatly reduces, in other αSyn overexpressing mice, the cytokine release by these cells after exposure to #Lipopolysaccharide > absence of substantial central and peripheral inflammation.
• [#Parkinson’s Disease] - #Enterobacteriaceae is increased in patients with PD and is associated with disease severity. - Its role as an αSyn cross-seeding agent, in the promotion of αSyn aggregation and worsening of motor symptoms, was documented in different models, such as C. elegans, Fisher rats, and another line of αSyn-overexpressing mice.
• [#Parkinson’s Disease] [#Escherichia coli] [#Fiber-free diet] - oral administration of E. coli to αSyn-overexpressing mice exacerbates PD-like pathologies, such as phosphorylated αSyn-positive structures and neurodegeneration, which are more pronounced in mice fed an FD diet.
• [1.15] [#Natural Nose microbiome, #Parkinson’s Disease] 
  - Chronic nasal dysbiosis induced by local inflammation can significantly enhance neurodegenerative damage of OSNs, which leads to an accumulation of misfolded aSyn. - Misfolded aSyn commonly appears in the olfactory bulb tissue and neuroepithelium samples of PD patients. - Olfactory dysfunction has been observed in the early phase of PD progression.
• [1.16] 
  - Supplementation of #Propionate protected neurons from α-syn-induced neurodegeneration.
• [#Parkinson’s Disease] [#Escherichia coli] - Among the 38 proneurodegenerative E. coli genes identified in the #Genome-wide screen, we previously characterized the genes responsible for producing the bacterial #Amyloid fibril #Curli, which could enter the host neurons to cross-seed the aggregation of α-syn and promote neurodegeneration.
• [1.17] [#Parkinson’s Disease] 
  - #Curcumin has further demonstrated protective effects against neurodegeneration in the A57Tα-synuclein model of PD by downregulating mTOR/p70S6 kinase (P70S6K) signaling and recovering macro autophagy

References Notes