So … if those are elevated, addressing the cause is the primary focus.
For most of us, we have normal levels, so the liver health part of this isn’t the benefit - the question is on the neurocognitive component, which I wish we had more evidence for.
Now for @John_Hemming who enjoys his ethanol … might be another mitigating action in addition to the citrate.
On UDCA seems like Vera-Health has much more to say, and many more references
Ursodeoxycholic acid (UDCA) has shown potential in addressing neurodegeneration through various mechanisms. UDCA is a bile acid that has been studied for its neuroprotective properties in several neurodegenerative diseases. It is known to cross the blood-brain barrier, making it a promising candidate for treating central nervous system disorders.
In Parkinson’s disease (PD), UDCA has been investigated for its ability to rescue mitochondrial function, a key factor in neurodegeneration. A study demonstrated that high-dose UDCA was safe and well-tolerated in early PD, with evidence of improved ATP hydrolysis in the midbrain, suggesting potential neuroprotective effects
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UDCA has also been studied in the context of GM2 gangliosidosis, a neurodegenerative disorder. It was found to diminish neurite atrophy and decrease pro-apoptotic signaling, indicating its role in alleviating endoplasmic reticulum stress and promoting neuronal survival
8
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Furthermore, UDCA and its derivative, tauroursodeoxycholic acid (TUDCA), have been shown to reduce prion protein conversion and neuronal loss in prion disease models. These compounds demonstrated neuroprotective effects by reducing astrocytosis and prolonging survival in prion-infected mice, highlighting their potential in treating protein misfolding diseases
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The modulation of apoptosis through the p53 pathway is another mechanism by which UDCA exerts its effects. It has been suggested that UDCA can modulate p53-triggered apoptosis, which is relevant in various neurodegenerative conditions
1
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Overall, UDCA shows promise as a therapeutic agent in neurodegenerative diseases due to its ability to modulate mitochondrial function, reduce protein misfolding, and influence apoptotic pathways. However, further research and larger clinical trials are needed to fully establish its efficacy and safety in these conditions.
References
- Solving neurodegeneration: common mechanisms and strategies for new treatments
Molecular Neurodegeneration
Wareham et al.
121 citations
2022
Major areas of mechanistic overlap between neurodegenerative diseases of the central nervous system: neuroinflammation, bioenergetics and metabolism, genetic contributions, and neurovascular interactions are discussed.
Open Access
Highly Influential Journal
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2. The Q/R editing site of AMPA receptor GluA2 subunit acts as an epigenetic switch regulating dendritic spines, neurodegeneration and cognitive deficits in Alzheimer’s disease
Molecular Neurodegeneration
Wright et al.
9 citations
2023
Eliminating unedited GluA2(Q) expression in AD mice prevented dendritic spine loss and hippocampal CA1 neurodegeneration as well as improved working and reference memory in the radial arm maze and revealed increased spine density in non-AD mice with exonically encoded Glu a2(R) as compared to their wild-type littermates, suggesting an unexpected and previously unknown role for un edited GLUA2 (Q) in regulating dendrites.
Open Access
Highly Influential Journal
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3. BIN1 is a key regulator of proinflammatory and neurodegeneration-related activation in microglia
Molecular Neurodegeneration
Sudwarts et al.
39 citations
2022
The consensus from in vitro and in vivo findings showed that loss of Bin1 impaired the ability of microglia to mount type 1 interferon responses to proinflammatory challenge, particularly the upregulation of a critical type 1 immune response gene, Ifitm3 .
Open Access
Highly Influential Journal
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4. Mammalian/mechanistic target of rapamycin (mTOR) complexes in neurodegeneration
Molecular Neurodegeneration
Querfurth et al.
131 citations
2021
Beyond rapamycin; an mTOR inhibitor, there are rapalogs having greater tolerability and micro delivery modes, that hold promise in arresting these age dependent conditions.
Open Access
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5. cGAS-STING triggers inflammaging-associated neurodegeneration
Molecular Neurodegeneration
Izquierdo et al.
0 citations
2023
Open Access
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6. Excitotoxicity, calcium and mitochondria: a triad in synaptic neurodegeneration
Translational Neurodegeneration
Verma et al.
169 citations
2022
Evidence for sublethal excitatory injuries in relation to neurodegeneration associated with Parkinson’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis and Huntington’s disease is reviewed and strategies for normalizing the flux of calcium into and out of the mitochondrial matrix are discussed, thereby preventing excitotoxic dendritic loss.
Open Access
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7. A Double-Blind, Randomized, Placebo-Controlled Trial of Ursodeoxycholic Acid (UDCA) in Parkinson’s Disease.
Movement Disorders
Payne et al.
14 citations
2023
High-dose UDCA is safe and well tolerated in early PD and midbrain 31 P-MRS demonstrated an increase in both Gibbs free energy and inorganic phosphate levels in the UDCA treatment group compared to placebo, reflecting improved ATP hydrolysis.
Open Access
Influential Journal
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8. Ursodeoxycholic Acid Binds PERK and Ameliorates Neurite Atrophy in a Cellular Model of GM2 Gangliosidosis
International Journal of Molecular Sciences
Morales et al.
2 citations
2023
It is found that UDCA significantly diminished the neurite atrophy induced by GM2 accumulation in primary neuron cultures, suggesting a direct interaction between UDCA and the cytosolic domain of PERK, which promotes kinase phosphorylation and dimerization.
Open Access
Influential Journal
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9. Glycoursodeoxycholic Acid Reduces Matrix Metalloproteinase-9 and Caspase-9 Activation in a Cellular Model of Superoxide Dismutase-1 Neurodegeneration
Molecular Neurobiology
Vaz et al.
53 citations
2014
Data highlight caspase-9 and MMP-9 activation as key pathomechanisms in ALS and GUDCA as a promising therapeutic strategy for slowing disease onset and progression.
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10. The role of p53 in apoptosis.
Discover medicine
Amaral et al.
347 citations
2010
It is suggested that the finely tuned, complex control of p53 by Mdm-2 (mouse double minute-2, an oncoprotein) is a key step in UDCA modulation of p52-triggered apoptosis, with particular emphasis on potential benefits of UDCA.
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11. Bile Acids Reduce Prion Conversion, Reduce Neuronal Loss, and Prolong Male Survival in Models of Prion Disease
Journal of Virology
Cortez et al.
49 citations
2015
It is demonstrated that TUDCA and UDCA substantially reduced PrP conversion in cell-free aggregation assays, as well as in chronically and acutely infected cell cultures, and this effect occurs in prion disease, with an added mechanistic target of upstream prion seeding.
Open Access
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12. Targeting the p53 pathway of apoptosis.
Current pharmaceutical design
Amaral et al.
62 citations
2010
Recent developments of p53-induced apoptosis in human diseases are highlighted, and controversies arising from the double-edge sword of targeting p53 in disease are discussed.
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13. Role of neuroinflammation in neurodegeneration development
Signal Transduction and Targeted Therapy
Zhang et al.
259 citations
2023
The factors affecting neuroinflammation and the major inflammatory signaling pathways involved in the pathogenicity of neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and Amyotrophic lateral sclerosis are reviewed.
Open Access
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