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. 2025 Mar 29;34(11):2601-2610.
doi: 10.1007/s10068-025-01872-5. eCollection 2025 Jul.

Effect of bovine milk-derived peptide on SNAP-25 of the neurotransmitter system in treating the sialorrhoea in chronic neurological diseases

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Effect of bovine milk-derived peptide on SNAP-25 of the neurotransmitter system in treating the sialorrhoea in chronic neurological diseases

Jency Roshni et al. Food Sci Biotechnol. .

Abstract

Sialorrhea is a prominent symptom of chronic neurological disorders like amyotrophic lateral sclerosis, Parkinson's disease, motor neuron disease, cerebral palsy, and stroke. Synaptosome-Associated Protein-25 (SNAP-25) plays a key role in triggering involuntary saliva secretion. This study aimed to identify SNAP-25-targeting bovine milk-derived peptides to mitigate sialorrhea, using computational and quantum atomistic simulation approach. Among 8559 bovine milk-derived peptides, 8499 were non-toxic, 7749 non-allergenic, 911 with blood-brain barrier crossing potential, and 175 with cell-penetrating capabilities. Using HAPPENN program, 20 non-hemolytic peptides were screened, while PeptideRanker predicted two physiologically active peptides. Protein-peptide docking followed by de novo structural modeling showed that CMPTFQFFK has a stronger inhibitory affinity (- 7.45 kcal/mol) for SNAP-25 than botulinum toxin. Additionally, dynamic simulations, free energy and quantum chemical studies confirmed the stability of CMPTFQFFK's with SNAP-25. Our study recommends CMPTFQFFK as a potential inhibitor of SNAP-25 for sialorrhea treatment, with further in vitro testing needed to confirm efficacy.

Keywords: Botulinum toxin A; Bovine milk; Peptides; SNAP-25; Sialorrhea.

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Conflict of interest statement

Conflict of interestThere are no conflicts to declare.

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