Thiamine deficiency review : endoplasmic reticulum & protein misfolding

[aspergerian13]

Article:

ncbi.nlm.nih.gov/pmc/articl...

See in text around citations 90, 91...

[aspergerian13]

By the way, the researchers cite Costantini.

Thiamine Deficiency and Neurodegeneration: The Interplay among Oxidative Stress, Endoplasmic Reticulum Stress and Autophagy.

Dexiang Liu, Zunji Ke, and Jia Luo.

[Kia17]

👍👍

“Insufficient levels of thiamine causes neurological and metabolic disorders which may be corrected by thiamine administration.” We all know about the TD effects on neurological diseases. We must understand its effects on metabolic disorders as well where the issue of Insulin resistance comes to light. Technically Thiamine adjust insulin sensitivity.

[park_bear]

Good find.

" We investigated the effect of TD[Thiamine deficiency] on the ER[Endoplasmic reticulum] with transmission electron microscopy and showed that TD causes an abnormality in ER structure [97]. We further demonstrated that TD up-regulates several markers of ER stress in the brain and cultured neurons, such as GRP78, CHOP and the phosphorylation of eIF2α [97]. Furthermore, TD activates an ER stress-regulated caspase, caspase-12 and blocking the caspase-12 activation significantly alleviates TD-induced neuronal death[97]. We have also shown that TD activates double stranded RNA-activated protein kinase (PKR) which is also believed to play an important role in ER stress [97, 98]. These findings suggest that ER stress may underlie TD-induced damage to the CNS."

[MBAnderson]

Can you remind me why we are taking thiamine instead of benfotiamine?

[Gioc in reply to MBAnderson]

I think Bettendorff said that.

researchgate.net/publicatio...

[aspergerian13 in reply to MBAnderson]

Benfotiamine remains in the periphery, outside the brain.

[aspergerian13]

See also:

The ER retention protein RER1 promotes alpha-synuclein degradation via the proteasome : 2017 : endoplasmic reticulum.

journals.plos.org/plosone/a...

α-Synuclein binds to the ER–mitochondria tethering protein VAPB to disrupt Ca2+ homeostasis and mitochondrial ATP production : endoplasmic reticulum : 2017.

ncbi.nlm.nih.gov/pmc/articl...

[aspergerian13]

And more:

ER stress response plays an important role in aggregation of α-synuclein | 2010 : endoplasmic reticulum.

molecularneurodegeneration....

α-Synuclein: A Multifunctional Player in Exocytosis, Endocytosis, and Vesicle Recycling : 2019.

ncbi.nlm.nih.gov/pmc/articl...

[aspergerian13 in reply to aspergerian13]

TD is a player:

Thiamine deficiency induces endoplasmic reticulum stress and oxidative stress in human neurons derived from induced pluripotent stem cells.

Xin Wang, Mei Xu, [...], and Jia Luo.

ncbi.nlm.nih.gov/pmc/articl...

[aspergerian13]

α-synuclein induces apoptosis of astrocytes by causing dysfunction of the endoplasmic reticulum-Golgi compartment : GDNF : 2018

ncbi.nlm.nih.gov/pmc/articl...

...it was also demonstrated, in a primary neuronal-astroglial co-culture system, that the overexpression of α-syn significantly decreased the levels of glia-derived neurotrophic factor (GDNF) and partly inhibited neurite outgrowth. Although direct evidence is currently lacking, it was proposed that dysfunction of the ER-Golgi compartment in astrocytes overexpressing α-syn may lead to a decline of GDNF levels, which in turn would suppress neurite outgrowth.

[MarionP]

That's nice, but what are we to DO about it?