Trehalose has been accused of causing dangers to gut biome but more recent info appears to be the opposite. Will you please help me evaluate Trehalose? I think it may be good for us.
..., we found that trehalose at low concentration disaggregates preformed A53T AS protofibrils and fibrils into small aggregates or even random coil structure, while trehalose at high concentration slows down the structural transition into β-sheet structure and completely prevents the formation of mature A53T AS fibrils. Further work in vivo will be needed to evaluate its potential as a novel strategy for treating PD.
In a macaque model of PD, also based on delivery of AAV1/2-hourA53T-aSyn to the SN, trehalose (2.67 g/kg per day, by mouth), administered for 142 days, produced higher striatal dopamine (by 39%) and dopamine transporter levels (by 50%), compared with macaques receiving vehicle. In neither model did trehalose treatment prevent loss of tyrosine hydroxylase (TH) positive (TH+ve) cells in the SN or alter α-synuclein levels in the striatum. These studies demonstrated that trehalose reduces striatal dopaminergic deficits in a rodent and macaque model of synucleinopathy in PD.
Divide macaque dosage by three to arrive at human dosage = .9g/kg. That ends up being a lot - a couple of ounces for a 60 kilogram person.
Macaques receiving AAV1/ 2-hourA53T-aSyn and treated with trehalose (2.67 g/kg per day) had significantly higher putamenal dopamine (110 6 8 compared to 79 6 13 ng/mg protein) (Fig. 4A) and DAT (411 6 48 compared with 274 6 36 nCi/g tissue) (Fig. 4C) levels compared with macaques receiving AAV1/2-hourA53T-aSyn and vehicle. Trehalose treatment did not significantly alter putamenal HVA or DOPAC levels or putamenal dopamine turnover. Moreover, trehalose treatment did not alter the number of TH1ve cells in the SN, the amount of aSyn in the striatum, or motor activity.
Trehalose as a promising therapeutic candidate for the treatment of Parkinson's disease. In this review, we briefly summarize the role of aberrant autophagy in PD and the underlying mechanisms that lead to the development of this disease. We also discuss reports that used trehalose to counteract the neurotoxicity in PD, focusing particularly on
the autophagy promoting, protein stabilization, and anti‐neuroinflammatory effects
of trehalose
Macaque results. White = healthy. Blue = PD untreated. Orange = PD + trehalose
Trehalose intake by Lewy body disease model mice increased levels of several chaperone molecules, such as HSP90 and SigmaR1, suggesting its roles in protein folding76. Oxygen-glucose deprivation (OGD) inhibits proteasome activity via suppression of both oxidative stress and ER stress. Trehalose inhibited OGD-induced autophagy while preserving proteasome activity86.
The stress granule formation is initiated by recruitment of eukaryotic initiation factor 2 (eIF2) to form eIF2-GTP-tRNAiMet ternary complex. Many proteins in the stress granules are dysregulated in human diseases, such as ALS. Prolonged accumulation of the stress granules may lead to increased protein aggregation and the pathogenesis of neurodegenerative diseases. Trehalose efficiently promoted the stress granule disassembly via the p-eIF2α pathway, suggesting that neuroprotective effects of trehalose may include the regulation of the stress granules87.
It’smorecomplex than just autophagy or no autophagy.
D. In our latest study, addition of trehalose into the culture medium of SH-SY5Y cells increased α-synuclein aggregation and lysosomal integrity was also impaired80. Curiously, there was little correlation between protein aggregation and cell toxicity when trehalose was present, suggesting that the aggregates formed under trehalose treatment conditions were not toxic or that trehalose protected cells from aggregate toxicity. Mouse primary cortical neurons exposed to pre-formed fibrils (PFF) of α-synuclein had shown an increased abundance of phosphorylated S129 form and reduced cell viability88. Trehalose failed to remove α-synuclein aggregates in these cells. However, it increased basal cell viability compared to non-treated cells. These results suggest that protective effects of trehalose may act independently from its effects on protein aggregation.
GUT it’s the effect on the GUT
What might be the mechanism of neuroprotection by trehalose? Contrary to the direct uptake of trehalose in culture, trehalose treated to animals in drinking water is likely to be hydrolyzed by trehalase enzyme in the gut. Even if some trehalose enters the blood stream, there is the blood–brain barrier (BBB) that limits the access of trehalose to the brain.
We propose that trehalose intake exerts neuroprotective effects in neurodegenerative disease models through a direct or indirect mechanism, which may involve the gut microbiota.
Based on this info from the link above and corresponding quotes, it is my takeaway that no, a couple ounces is not needed bc it’s ability to induce autophagy is poorly understood and it is believed that it’s effect on the gut might be what is indirectly promoting autophagy.
So, I take 1-2 teaspoons a few days a week bc I think it appears safe, tastes yummy, and I hope it is helping my gut .
The gut-brain connection in the pathogenicity of Parkinson disease: Putative role of autophagy 2021 pubmed.ncbi.nlm.nih.gov/338...
"Parkinson disease (PD) is a progressive movement functionality disorder resulting in tremor and inability to execute voluntary functions combined with the preponderant non-motor disturbances encompassing constipation and gastrointestinal irritation. Despite continued research, the pathogenesis of PD is not yet clear. The available class of drugs for effective symptomatic management of PD includes a combination of levodopa and carbidopa. In recent past, the link between gut with PD has been explored. According to recent preclinical evidence, pathogens such as virus or bacterium may initiate entry into the gut via the nasal cavity that may aggravate lewy pathology in the gut that eventually propagates and progresses towards the brain via the vagus nerve resulting in the prodromal non-motor symptoms. Additionally, experimental evidence also suggests that alpha-synuclein misfolding commences at a very early stage in the gut and is transported via the vagus nerve prior to seeding PD pathology in the brain. However, this progression and resultant deterioration of the neurones can effectively be altered by an autophagy inducer, Trehalose, although the mechanism behind it is still enigmatic. Hence, this review will mainly focus on analysing the basic components of the gut that might be responsible for aggravating lewy pathology, the mediator(s) responsible for transmission of PD pathology from gut to brain and the important role of trehalose in ameliorating gut dysbiosis related PD complications that would eventually pave the way for therapeutic management of PD. "
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