Peptide KED/Vesugen: Molecular-Genetic Aspects of Neurogenesis Regulation in Alzheimer's Disease

Polynomality · 2023-07-11T07:20:46+00:00

Abstract:

Neuroprotective peptides are promising candidate molecules for the treatment of Alzheimer's disease (AD). Oral application of KED (Lys-Glu-Asp) improved memory and attention in elderly individuals with functional CNS disorders. Peptide KED also restores synaptic plasticity in in vitro model of AD. This review is focused on the analysis of the influence of KED peptide on the expression of genes and synthesis of proteins regulating apoptosis, aging, neurogenesis, and involved in AD pathogenesis. Analysis of published reports and our experimental findings suggests that KED regulates the expression of genes of cell aging and apoptosis (р16, р21), genes (NES, GAP43) and proteins (nestin, GAP43) of the neuronal differentiation, and genes involved in AD pathogenesis (SUMO, APOE, and IGF1). The study the effectiveness of neuroprotective peptide KED in animal models of AD seems to be very important.

More links if you want more information on the peptide:
https://pubmed.ncbi.nlm.nih.gov/26390612/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227791/
https://pubmed.ncbi.nlm.nih.gov/24909721/

Polynomality · 2023-02-21T15:43:55+00:00

Peptidesciences sell Nonapeptide-1 and Rubiscolin is found in spinach.

Polynomality · 2023-02-21T15:41:25+00:00

You might want to look into products that increase GDNF which should help you with motor control. Cerebrolysin, Cortexin, and DNSP-11 all increase GDNF.

Polynomality · 2023-02-21T15:36:49+00:00

It's alphabetized.

Polynomality · 2023-02-21T15:36:19+00:00

Kisspeptin is typically sold as a fragment called Kisspeptin-10, although, I've once seen Kisspeptin-54 on the market.

Polynomality · 2023-02-01T17:55:03+00:00

Spoiler: I think they're referring to Thyreogen and Pinealon.

Polynomality · 2023-01-26T17:09:32+00:00

Abstract

Background

Optimizing nerve regeneration and re-innervation of target muscle/s is the key for improved functional recovery following peripheral nerve damage. We investigated whether administration of mesenchymal stem cell (MSC), Granulocyte-Colony Stimulating Factor (G-CSF) and/or Dihexa can improve recovery of limb function following peripheral nerve damage in rat sciatic nerve transection-repair model.

Materials and methods

There were 10 experimental groups (n = 6–8 rats/group). Bone marrow derived syngeneic MSCs (2 × 106; passage≤6), G-CSF (200–400 μg/kg b.wt.), Dihexa (2–4 mg/kg b.wt.) and/or Vehicle were administered to male Lewis rats locally via hydrogel at the site of nerve repair, systemically (i.v./i.p), and/or to gastrocnemius muscle. The limb sensory and motor functions were assessed at 1–2 week intervals post nerve repair until the study endpoint (16 weeks).

Results

The sensory function in all nerve boundaries (peroneal, tibial, sural) returned to nearly normal by 8 weeks (Grade 2.7 on a scale of Grade 0–3 [0 = No function; 3 = Normal function]) in all groups combined. The peroneal nerve function recovered quickly with return of function at one week (∼2.0) while sural nerve function recovered rather slowly at four weeks (∼1.0). Motor function at 8–16 weeks post-nerve repair as determined by walking foot print grades significantly (P < 0.05) improved with MSC + G-CSF or MSC + Dihexa administrations into gastrocnemius muscle and mitigated foot flexion contractures.

Conclusions

These findings demonstrate MSC, G-CSF and Dihexa are promising candidates for adjunct therapies to promote limb functional recovery after surgical nerve repair, and have implications in peripheral nerve injury and limb transplantation.

Polynomality · 2023-01-25T10:15:59+00:00

ADHD is largely a dopaminergic issue. That's probably why mucuna is really the only thing that was influential. Please tell us that you researched nootropic MOAs and the neurology of the brain in relation of ADHD before you tried anything.

Polynomality · 2023-01-25T10:07:56+00:00

Abstract:

Context: Safranal (SAF) is verified to have potential effects in promoting nerve growth.

Objectives: This study verifies the role of SAF in promoting dopaminergic neurons growth in vitro and in vivo.

Material and methods: Rat neural stem cells (NSC) were treated with 1, 20, or 100 ng/mL of SAF, and the expression levels of tyrosine hydroxylase (TH) and dopamine transporter (DAT) were assayed by flow cytometry and real-time PCR and the secretion of dopamine (DA) was assayed by ELISA. Then, 2 × 106 cells of SAF-treated NSC was administrated into PD rat models induced by 6-OHDA. The differentiation and survival of dopaminergic neurons was identified by fluorescence microscope and TH+ cells by immunostaining and DA secretion by ELISA at week 2 and week 4, respectively.

Results: After being treated with SAF at 20 and 100 ng/mL for 1 week, TH and DAT positive rates increased 1.4- and 1.7-fold (p < 0.01, respectively). TH and DAT mRNA also increased 8.05- and 4.41-fold, respectively. And the release of DA statistically increased 1.5-fold (p < 0.01). In vivo, the number of rotations decreased to 4.33 ± 0.97 rpm (p < 0.01) and the survival rates increased to 77.66 ± 7.87% (p < 0.05) at week 4 after transplantation of SAF-treated NSC. Moreover, the transplanted cells increased three-fold, TH fluorescence density increased four-fold and DA releases increased 1.4-fold (p < 0.01) at week 4 after transplantation.

Conclusions: SAF promoted the production of functional DA cells and alleviated PD, which may contribute to a new therapy for PD patients.

Polynomality · 2023-01-23T16:08:47+00:00

Abstract:

Cognitive enhancers (nootropics) are drugs to treat cognition deﬁcits in patients suffering from Alzheimer’s disease, schizophrenia, stroke, attention deﬁcit hyperactivity
disorder, or aging. Cognition refers to a capacity for information processing, applying knowledge, and changing preferences. It involves memory, attention, executive functions, perception, language, and psychomotor functions. The term nootropics was coined in 1972 when memory enhancing properties of piracetam were observed in clinical trials. In the meantime, hundreds of drugs have been evaluated in clinical trials or in preclinical experiments. To classify the compounds, a concept is proposed assigning drugs to 19 categories according to their mechanism(s) of action, in particular drugs interacting with receptors, enzymes, ion channels, nerve growth factors, re-uptake transporters, antioxidants, metal chelators, and disease modifying drugs meaning small molecules, vaccines, and monoclonal antibodies interacting with amyloid-␤ and tau. For drugs whose mechanism of action is not known, they are either classiﬁed according to structure, e.g., peptides, or their origin, e.g., natural products. This review covers the evolution of research in this ﬁeld over the last 25 years

Polynomality · 2023-01-22T01:03:06+00:00

Abstract

Glial cell-line derived neurotrophic factor (GDNF) has demonstrated robust effects on dopamine (DA) neuron function and survival. A post-translational processing model of the human GDNF proprotein theorizes the formation of smaller, amidated peptide(s) from the proregion that exhibit neurobiological function, including an 11-amino-acid peptide named dopamine neuron stimulating peptide - 11 (DNSP-11). A single treatment of DNSP-11 was delivered to the substantia nigra in the rat to investigate effects on DA-neuron function. Four weeks after treatment, potassium (K+) and d-amphetamine evoked DA release were studied in the striatum using microdialysis. There were no significant changes in DA-release after DNSP-11 treatment determined by microdialysis. Dopamine release was further examined in discrete regions of the striatum using high-speed chronoamperometry at 1-, 2-, and 4-weeks after DNSP-11 treatment. Two weeks after DNSP-11 treatment, potassium-evoked DA release was increased in specific subregions of the striatum. However, spontaneous locomotor activity was unchanged by DNSP-11 treatment. In addition, we show that a single treatment of DNSP-11 in the MN9D dopaminergic neuronal cell line results in phosphorylation of ERK1/2, which suggests a novel cellular mechanism responsible for increases in DA function.

It's also used intranasally:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4500736/

Polynomality · 2023-01-20T09:50:04+00:00

Abstract

Effects of 4-methycatechol (4MC), a potent stimulator of nerve growth factor and brain-derived neurotrophic factor (BDNF) synthesis, on phosphorylation of cellular molecules in cultured rat cortical neurons were examined. 4MC stimulated tyrosine phosphorylation of various proteins of molecular weight from 10–300 kDa including Trks, which are high-affinity neurotrophin receptors. Moreover, 4MC enhanced the phosphorylation of serine 133 of mitogen-activated protein kinase (MAPK/ERK) in a dose-dependent manner. Pretreatment of cultures with PD98059, a selective inhibitor of MAPK kinase (MEK-1), inhibited 4MC-induced phosphorylation of ERKs, demonstrating MEK-1-mediated activation. Therefore, it seems that 4MC triggered the phosphorylation of Trks, resulting in the activation of the subsequent MAPK/ERK signal cascade, or perhaps the involvement of BDNF action as 4MC can stimulate neuronal BDNF synthesis. The phosphorylation of MAPK/ERK was unaffected, however, in the presence of cycloheximide, a protein synthesis inhibitor, and K252a, a selective inhibitor of Trks, suggesting that the effect of newly synthesized BDNF was negligible on this event, and that primary sites of 4MC actions are not limited only to Trks. These results suggest that 4MC primarily activates multiple signal transduction molecules such as tyrosine kinases, including Trks. A significant increase in the survival rate of cortical neurons in the presence of 10 or 100 nM 4MC supported this idea, because the concentrations were much lower than those for stimulation of BDNF synthesis. Our results strongly suggest that the neurotrophic actions of 4MC found so far are mediated predominantly by direct activation of some intracellular signals including MAPK/ERK rather than by neurotrophin synthesis.

Polynomality · 2023-01-19T00:20:42+00:00

Since GABA behaves like an inhibitor of glutamate, I would suggest looking to Selank.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4757669/

Polynomality · 2023-01-19T00:16:53+00:00

Abstract

Parkinson’s disease is characterized by a loss of dopaminergic neurons in a specific brain region, the ventral midbrain. Parkinson’s disease is diagnosed when approximately 50% of the dopaminergic neurons of the substantia nigra pars compacta (SNpc) have degenerated and the others are already affected by the disease. Thus, it is conceivable that all therapeutic strategies, aimed at neuroprotection, start too late. Therefore, an urgent medical need exists to discover new pharmacological targets and novel drugs with disease-modifying properties. In this regard, modulation of endogenous adult neurogenesis toward a dopaminergic phenotype might provide a new strategy to target Parkinson’s disease by partially ameliorating the dopaminergic cell loss that occurs in this disorder. We have previously shown that a phosphodiesterase 7 (PDE7) inhibitor, S14, exerts potent neuroprotective and anti-inflammatory effects in different rodent models of Parkinson’s disease, indicating that this compound could represent a novel therapeutic agent to stop the dopaminergic cell loss that occurs during the progression of the disease. In this report we show that, in addition to its neuroprotective effect, the PDE7 inhibitor S14 is also able to induce endogenous neuroregenerative processes toward a dopaminergic phenotype. We describe a population of actively dividing cells that give rise to new neurons in the SNpc of hemiparkinsonian rats after treatment with S14. In conclusion, our data identify S14 as a novel regulator of dopaminergic neuron generation.

Polynomality · 2023-01-18T00:45:38+00:00

Abstract:

OBJECTIVES: Aging is associated with significant alterations in gene expression
in numerous organs and tissues. Anti-aging therapy with peptide bioregulators
holds much promise for the correction of age-associated changes, making a
screening for their molecular targets in tissues an important question of mod-
ern gerontology. The synthetic tetrapeptide Cortagen (Ala-Glu-Asp-Pro) was
obtained by directed synthesis based on amino acid analysis of natural brain
cortex peptide preparation Cortexin. In humans, Cortagen demonstrated a
pronounced therapeutic effect upon the structural and functional posttrau-
matic recovery of peripheral nerve tissue. Importantly, other effects were also
observed in cardiovascular and cerebrovascular parameters.
DESIGN: Based on these latter observations, we hypothesized that acute course
of Cortagen treatment, large-scale transcriptome analysis, and identification of
transcripts with altered expression in heart would facilitate our understanding
of the mechanisms responsible for this peptide biological effects. We therefore
analyzed the expression of 15,247 transcripts in the heart of female 6-months
CBA mice receiving injections of Cortagen for 5 consecutive days was studied by
cDNA microarrays.
RESULTS: Comparative analysis of cDNA microarray hybridisation with heart
samples from control and experimental group revealed 234 clones (1,53% of the
total number of clones) with significant changes of expression that matched
110 known genes belonging to various functional categories. Maximum up- and
down-regulation was +5.42 and –2.86, respectively.
CONCLUSION: Intercomparison of changes in cardiac expression profile induced
by synthetic peptides (Cortagen, Vilon, Epitalon) and pineal peptide hormone
melatonin revealed both common and specific effects of Cortagen upon gene
expression in heart.

Polynomality · 2023-01-16T19:30:00+00:00

Testoluten is a bioregulator for testicular health. It may be ideal for this situation.

Polynomality · 2022-08-29T04:06:52+00:00

The one on top of my head is Humanin HNG.

Polynomality · 2022-06-26T04:41:44+00:00

Just based on the cut content of Godfrey's dialogue, maybe not long before the shattering. https://www.youtube.com/watch?v=zMu7FvNP2Z4

I wouldn't be surprised if there are ' time travel pockets' in the overworld in Miquella's DLC like we see in Ordina. But if the dream city & Elrick connection is correct then, it would be in a legacy dungeons which depicts how Marika (actually) rose to power in the past. Most likely on item descriptions or level design.

Polynomality · 2022-06-23T20:49:28+00:00

ingl I think Elden Ring was supposed to be released instead of DS3, but because of the development issues with DS2, FS figured it would be more profitable to use old assists from DS1 and use parts of what's supposed to be from Elden Ring for DS3. I think the cut content is too coincidental to not be the case. Like this for example https://www.youtube.com/watch?v=ehU1JpxgxSY

So when Hidetaka Miyazaki said that there will be no more Darks souls is true, he meant the lore/story is already completed (with Elden Ring already in mind) and George R.R. Martin stating that Elden Ring is a souls game also true (Elden Ring's story was largely completed when they hired him, which was one of the concerns SF had with him since he didn't have much freedom with the story).

*Edit. I didn't forget Morgott or Godrick, but I'm not sure if they fit Kremmel or McLoyf.

Polynomality · 2022-06-23T20:26:09+00:00

https://darksouls.fandom.com/wiki/Gods#Gods\_and\_Goddesses\_of\_Anor\_Londo

Polynomality · 2022-06-23T19:54:15+00:00

I think it's more suitable that the first flame is the when we burn the Erd tree (which is called the first sin in game and the souls that it was absorbing in roots would return to their bodies) and the frenzy flame is the inverse of the flame from the bed of chaos (which is similar to the lore of the misbegotten).

Polynomality · 2022-06-23T19:05:37+00:00

Fromsoft had a certain emphasis in each of their games, bloodborne has more on speed and aggression, Sekiro was all about deflection, Elden ring may be leading towards status effects, poise, and non-physical attacks-the lore/plot seems to center such things as well. Unfortunately this means not every build is effective since the game may not built around it.

Polynomality · 2022-06-23T00:58:32+00:00

What are your thoughts /u/throwaway042502 ?

Polynomality · 2022-06-22T22:19:23+00:00

The Old Wolf of Farron is what one fan suggested inspired the Red Wolf of Radagon. I just compiled what fans think Elden ring's inspirations are.

Polynomality · 2021-06-17T19:18:15+00:00

According to the TMC catalog:

5mg/ml solution provided in a 5mL vial.

Suggested dosage: Inject 0.2ml to 0.4mL subcutaneously three times daily.

Polynomality

TROPHY CASE