Spadin, a Sortilin-derived peptide: a new concept in the antidepressant drug design

Heurteaux, Catherine; Mazella, Jean; Borsotto, Marc; Antipolis, Sophia

doi:10.1051/ocl.2011.0395

Cited by 1 publication

(2 citation statements)

References 27 publications

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“…Sortilin and TREK-1 genes have been implicated in depression due to their high expression in the cerebral structures, and a study has shown that TREK-1 activity was efficiently inhibited by spadin in CA3 hippocampal neurons in brain slices, cultured hippocampal pyramidal neurons, and COS-7 cells [ 52 ]. A subchronic treatment of the adult mouse hippocampus with spadin showed that it activated neurogenesis and transcription factor cAMP response element-binding protein (CREB), with direct inhibition of TREK-1, which caused increased neuron excitability during a forced swim test (FST) [ 53 ]. Furthermore, CREB mediates transcriptional responses to high levels of cAMP due to a chronic administration of antidepressant, thus triggering downstream targets such as the brain-derived growth factor (BDNF) [ 54 , 55 ].…”

Section: Discussionmentioning

confidence: 99%

“…Several peptides that have been reported with suitable biological activity such as antioxidant, anti-neurodegeneration, antidiabetic, and anti-inflammatory in ALS studies were selected for this analyses, these include: P5-Best [ 115 ]; peptide H3 [ 58 ]; NAP, ADNF-9, and humanin [ 116 ]; soy-deprestatin [ 117 ]; spadin [ 52 , 53 ]; pro-neuropeptide Y (PNY) (seq.30–64), calcitonin gene-related peptide 1 (CGP)(seq.83–119), substance P (SP) (seq.1–11), vasoactive intestinal peptide (VIP) (seq.125–152), proenkephalin-A (PEA) (seq.209–237), α-melanocyte-stimulating hormone (α-MSH) (seq.1–13), and phoenixin (PNX-14) all from Wei et al [ 66 ]; and LAVYPWT (as standard neuropeptides obtained from BIOPEP-UMW) ( supplementary Table S1 ) were obtained from various online databases and literature. The sequences were subjected to simulate enzymatic hydrolysis on the BIOPEP-UWM webserver using the combination of digestive enzymes chymotrypsin (EC 3.4.21.1), pepsin, pH 1.3 (EC 3.4.23.1), and trypsin (EC 3.4.21.4) [ 118 ].…”

Section: Methodsmentioning

confidence: 99%

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In Silico Exploration of Metabolically Active Peptides as Potential Therapeutic Agents against Amyotrophic Lateral Sclerosis

Fatoki

Chukwuejim

Udenigwe

et al. 2023

IJMS

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Amyotrophic lateral sclerosis (ALS) is regarded as a fatal neurodegenerative disease that is featured by progressive damage of the upper and lower motor neurons. To date, over 45 genes have been found to be connected with ALS pathology. The aim of this work was to computationally identify unique sets of protein hydrolysate peptides that could serve as therapeutic agents against ALS. Computational methods which include target prediction, protein-protein interaction, and peptide-protein molecular docking were used. The results showed that the network of critical ALS-associated genes consists of ATG16L2, SCFD1, VAC15, VEGFA, KEAP1, KIF5A, FIG4, TUBA4A, SIGMAR1, SETX, ANXA11, HNRNPL, NEK1, C9orf72, VCP, RPSA, ATP5B, and SOD1 together with predicted kinases such as AKT1, CDK4, DNAPK, MAPK14, and ERK2 in addition to transcription factors such as MYC, RELA, ZMIZ1, EGR1, TRIM28, and FOXA2. The identified molecular targets of the peptides that support multi-metabolic components in ALS pathogenesis include cyclooxygenase-2, angiotensin I-converting enzyme, dipeptidyl peptidase IV, X-linked inhibitor of apoptosis protein 3, and endothelin receptor ET-A. Overall, the results showed that AGL, APL, AVK, IIW, PVI, and VAY peptides are promising candidates for further study. Future work would be needed to validate the therapeutic properties of these hydrolysate peptides by in vitro and in vivo approaches.

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