Conditional triple amyloid precursor protein (APP) knockout was observed to induce hippocampus and corpus callosum morphology impairment, disruption of learning, and autism spectrum disorder (ASD)-like behavior in mice model, further elucidating the function of APP in brain development embopress.org/doi/full/10…
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📅︎ May 22 2021
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Controlled Ligand Exchange Between Ruthenium Organometallic Cofactor Precursors and a Naïve Protein Scaffold Generates Artificial Metalloenzymes Catalysing Transfer Hydrogenation

A ruthenium organometallic complex is transformed into an effective transfer hydrogenation catalyst upon exchanging ligands with a naïve protein. The direct coordination of protein sidechains to the metal is an underutilised feature in artificial metalloenzymes.

Abstract

Many natural metalloenzymes assemble from proteins and biosynthesised complexes, generating potent catalysts by changing metal coordination. Here we adopt the same strategy to generate artificial metalloenzymes (ArMs) using ligand exchange to unmask catalytic activity. By systematically testing RuII(η6‐arene)(bipyridine) complexes designed to facilitate the displacement of functionalised bipyridines, we develop a fast and robust procedure for generating new enzymes via ligand exchange in a protein that has not evolved to bind such a complex. The resulting metal cofactors form peptidic coordination bonds but also retain a non‐biological ligand. Tandem mass spectrometry and 19F NMR spectroscopy were used to characterise the organometallic cofactors and identify the protein‐derived ligands. By introduction of ruthenium cofactors into a 4‐helical bundle, transfer hydrogenation catalysts were generated that displayed a 35‐fold rate increase when compared to the respective small molecule reaction in solution.

https://ift.tt/3cpJmq8

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📅︎ Apr 26 2021
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Pulsed Telecommunication Signals of Non-ionizing Radiation Affect Amyloid Precursor Protein and α-Synuclein Metabolism in Non-neural Human Cells preprints.org/manuscript/…
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📅︎ Mar 06 2021
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What dictates the cleavage of Amyloid Precursor Protein to form toxic beta-amyloid fragments?

Hi all-

I understand that Amyloid precursor protein is cleaved collectively by alpha, beta, and gamma secretase, and this is what leads to the formation of the neurotoxic beta-amyloid fragment.

However, is it understood why this cleavage occurs? What drives these secretases to cleave APP in the first place?

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👤︎ u/Rexzolt99
📅︎ Feb 22 2021
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TIL Dietary Tryptophan can only be pushed into the brain by eating a high-carb, low-protein meal. Dietary tryptophan is a precursor for the neurotransmitters serotonin and melatonin

Super interesting stuff. This would explain why some depressed people crave carbs, its literally because they NEED carbs to boost serotonin levels. The mechanism by which this happens is really interesting and explained below.

Serotonin can't pass thru the BBB so there is no point in a serotonin supplement.

https://genesandnutrition.biomedcentral.com/articles/10.1007/s12263-009-0148-z

>Even if a dietary component is bioavailable, it may still not reach its active site in the target organ. For example, dietary tryptophan is an essential amino acid and precursor for the neurotransmitters serotonin and melatonin. Serotonin is not able to cross the BBB and centrally acting serotonin must be synthesised inside the central nervous system [25]. Circulating tryptophan is known to have some access through the BBB via the large neutral amino acid (LNAA) transporter.

>However, it must compete with other LNAAs for this transporter, and thus the ratio of tryptophan to the other LNAAs in plasma determines its ability to cross the BBB. This ratio can be increased in favour of tryptophan by the co-consumption of a carbohydrate-rich and protein-poor meal [47]. The mechanism is due to the acute carbohydrate ingestion inducing an insulin spike and the subsequent absorption of LNAAs, except for tryptophan, by muscle cells.

>Because there is relatively little tryptophan in dietary protein, as compared to the other LNAAs, the lack of dietary protein at the same time will further push the tryptophan/LNAA ratio in favour of tryptophan. Together, this reduces competition for the LNAA transporter, thus allowing a greater influx of tryptophan through the BBB (see [45] for detailed review).

>Using the example from above, tryptophan entry through the BBB and into the brain can be increased via the co-consumption of a carbohydrate-rich, protein-poor meal. As mentioned, tryptophan is the precursor to serotonin and increasing tryptophan levels in the brain leads to an increased serotonergic tone and an improvement of symptoms in vulnerable subjects under stress [46]. The production of serotonin from tryptophan first requires a hydroxylase step, forming 5-hydroxytryptophan which is then decarboxylated by the enzyme L-amino acid decarboxylase into serotonin [16].

>This biosynthetic pathway is analogous to the synthesis of dopamine from its precursor tyrosine. However, neither dopamine nor serotonin has access through the BBB (either in or out of the brain) [2

... keep reading on reddit ➡

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📅︎ Jul 31 2020
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In theory, could high protein diets alleviate some mental illnesses, as well as, supplementing with dopamine precursors?

I just read a couple research studies that suggest theres a correlation between protein and dopamine.

Curious if taking precursor supplementing l-tyrosine or phenylalanine could increase dopamine levels in people with low dopamine levels, in theory, or are supplements placebo?

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👤︎ u/Ocelot859
📅︎ Nov 13 2020
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Amyloid Precursor Protein Glycosylation is Different in the Alzheimer's Brain fightaging.org/archives/2…
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📅︎ Sep 27 2020
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Pulsed Telecommunication Signals of Non-ionizing Radiation Affect Amyloid Precursor Protein and α-Synuclein Metabolism in Non-neural Human Cells preprints.org/manuscript/…
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📅︎ Sep 05 2020
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Mobile phone electromagnetic radiation affects Amyloid Precursor Protein and α-synuclein metabolism in SH-SY5Y cells booksc.xyz/dl/74787432/5c…
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📅︎ Sep 05 2020
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Aβ-induced synaptic injury is mediated by presynaptic expression of amyloid precursor protein (APP) in hippocampal neurons biorxiv.org/content/10.11…
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👤︎ u/sburgess86
📅︎ Jul 20 2020
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Scientists identify a protein that can efficiently transport NMN, an NAD+ precursor currently being investigated for its effects against aging, directly into cells. medicine.wustl.edu/news/s…
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📅︎ Jan 07 2019
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Excessive consumption of BCAAs and diets high in protein may reduce lifespan, negatively impact mood and lead to weight gain. High levels of BCAAs in the blood compete with tryptophan, the precursor to serotonin, for transport into the brain. nature.com/articles/s4225…
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👤︎ u/vanderpyyy
📅︎ May 03 2019
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[ASAP] Direct Observation of Amorphous Precursor Phases in the Nucleation of Protein–Metal–Organic Frameworks

Journal of the American Chemical SocietyDOI: 10.1021/jacs.9b11371

https://ift.tt/3092QYb

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📅︎ Jan 09 2020
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Article:Psoriasis Improvement in Patients Using Glutathione-enhancing, Nondenatured Whey Protein Isolate [ie - not just whey protein]: A Pilot Study."This small single-center prospective, unblinded pilot study showed a positive clinical response in patients using a [Glutathione precursor supplement] ncbi.nlm.nih.gov/pmc/arti…
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📅︎ Dec 03 2018
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Amyloid Precursor Protein Binds to GABABR1 Receptors to Suppress Neuronal Transmission (in rats) - new study in Science explained by BrainPost brainpost.co/weekly-brain…
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📅︎ Feb 04 2019
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Amyloid Precursor Protein Binds to GABABR1 Receptors to Suppress Neuronal Transmission (in rats) - new study in Science explained by BrainPost brainpost.co/weekly-brain…
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📅︎ Feb 08 2019
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New study in mice demonstrates successful proof-of-concept that CRISPR/Cas9 may have the potential to be developed as a tool for gene therapy against Alzheimer’s Disease caused by specific generic mutations associated with increased the amyloid-β (Aβ) precursor protein. sciencedirect.com/science…
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👤︎ u/mvea
📅︎ Jun 03 2018
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Soluble Amyloid Precursor Protein Signals to Neural Stem Cells bioserendipity.com/2018/0…
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📅︎ Feb 08 2018
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Controlled Ligand Exchange Between Ruthenium Organometallic Cofactor Precursors and a Naïve Protein Scaffold Generates Artificial Metalloenzymes Catalysing Transfer Hydrogenation

A ruthenium organometallic complex is transformed into an effective transfer hydrogenation catalyst upon exchanging ligands with a naïve protein. The direct coordination of protein sidechains to the metal is an underutilised feature in artificial metalloenzymes.

Abstract

Many natural metalloenzymes assemble from proteins and biosynthesised complexes, generating potent catalysts by changing metal coordination. Here we adopt the same strategy to generate artificial metalloenzymes (ArMs) using ligand exchange to unmask catalytic activity. By systematically testing RuII(η6‐arene)(bipyridine) complexes designed to facilitate the displacement of functionalised bipyridines, we develop a fast and robust procedure for generating new enzymes via ligand exchange in a protein that has not evolved to bind such a complex. The resulting metal cofactors form peptidic coordination bonds but also retain a non‐biological ligand. Tandem mass spectrometry and 19F NMR spectroscopy were used to characterise the organometallic cofactors and identify the protein‐derived ligands. By introduction of ruthenium cofactors into a 4‐helical bundle, transfer hydrogenation catalysts were generated that displayed a 35‐fold rate increase when compared to the respective small molecule reaction in solution.

https://ift.tt/3cpJmq8

👍︎ 2
💬︎
📅︎ Mar 26 2021
🚨︎ report
Controlled Ligand Exchange Between Ruthenium Organometallic Cofactor Precursors and a Naïve Protein Scaffold Generates Artificial Metalloenzymes Catalysing Transfer Hydrogenation

Many natural metalloenzymes assemble from proteins and biosynthesised complexes, generating potent catalysts by changing metal coordination. Here we adopt the same strategy to generate artificial metalloenzymes using ligand exchange to unmask catalytic activity. By systematically testing Ru(II)(η 6 ‐arene)(bipyridine) complexes designed to facilitate the displacement of functionalised bipyridines, we develop a fast and robust procedure for generating new enzymes via ligand exchange in a protein that has not evolved to bind such a complex. The resulting metal cofactors form peptidic coordination bonds but also retain a non‐biological ligand. Tandem mass spectrometry and 19 F NMR spectroscopy were used to characterise the organometallic cofactors and identify the protein‐derived ligands. By introduction of ruthenium cofactors into a 4‐helical bundle, transfer hydrogenation catalysts were generated that displayed a 35‐fold rate increase when compared to the respective small molecule reaction in solution.

https://ift.tt/3kd9zKF

👍︎ 2
💬︎
📅︎ Feb 22 2021
🚨︎ report
In theory, could high protein diets alleviate some mental illnesses, as well as, supplementing with dopamine precursors?

I just read a couple research studies that suggest theres a correlation between protein and dopamine.

Curious if taking precursor supplementing l-tyrosine or phenylalanine could increase dopamine levels in people with low dopamine levels, in theory, or are supplements placebo?

👍︎ 7
💬︎
👤︎ u/Ocelot859
📅︎ Nov 13 2020
🚨︎ report

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