PE-22-28 Dosing Protocol: Neuroplasticity Guide

Despite the large number of available studies, a high clinical, statistical, and methodological heterogeneity was observed. More methodologically rigorous studies are needed to clarify the effectiveness of each protocol and modality of intervention.

Limitations: No placebo control reported. Review article — no new primary data.

From 89 studies (mean follow-up: 5.2 years), conversion risk was 41.5% (38.3%-44.7%) in clinical and 27.0% (22.0%-32.0%) in population-based studies, with Alzheimer's dementia as the most common outcome. Stability rates were 49.3% (clinical) and 49.8% (population).

Limitations: Animal study only — human translation uncertain. Review article — no new primary data.

Finally, our findings revealed that mice lacking TREK-1 gained more fat mass and had worse glucose tolerance when fed a high-fat diet (HFD) compared to the wild-type controls. The findings demonstrate that increase of the membrane potential at adipocytes through the downregulation of TREK-1 can influence the progression of adipogenesis.

Limitations: Animal study only — human translation uncertain.

The literature review for this guideline included studies published up to November 2023. More than 1000 peer-reviewed publications were included, covering the following.

Limitations: No placebo control reported.

The CCDDs using a Minimum Core Test (MCT) significantly increased from 45.7% in 2015 to the current 57.1%. Territorial CCDDs using MCT significantly increased from 24.9% in 2015 to 37% in 2022 (p = 0.004).

Limitations: No placebo control reported.

In addition, Mini-Spadin promotes beta-cell proliferation, suggesting its possible regenerative effect. This study highlights new possible roles of PE in pancreatic beta-cell survival and its derivatives as pharmacological tools against diabetes.

Limitations: Animal study only — human translation uncertain.

Finally, enhanced neurogenesis and synaptogenesis contributed to the beneficial effects of mini-spadin against stroke and PSD. This work reveals the first evidence that the modulation of TREK-1 channels in the early and chronic phases of stroke as well as the stimulation of brain plasticity by mini-spadin could play a key role in its brain protective effects against stroke and its deleterious consequences such as PSD.

Limitations: No placebo control reported.

Shortened spadin analogs present increased inhibition potency for TREK-1, an improved AD activity, and prolonged in vivo bioavailability. Finally, we also discuss about other inhibitors of TREK-1 channels with a proven efficacy in treating depression in the clinic, such as fluoxetine.

Limitations: No placebo control reported. Review article — no new primary data.

Finally, the action duration of PE 22-28 and its analogs was largely improved in comparison with that of spadin, up to 23 h instead of 7 h. Taken together, our results demonstrated that PE 22-28 and its derivatives represent other promising molecules that could be an alternative to spadin in the treatment of depression.

Limitations: Animal study only — human translation uncertain.

As a putative bioactive peptide, we have evaluated its autocrine effect by the use of spadin on 3T3-L1 adipocytes by performing glucose uptake and signalling experiments. Any effect was measured on adipocytes indicating that the use of spadin as an antidepressant would have no side effects on adipocyte physiology.

Limitations: Animal study only — human translation uncertain.