The Therapeutic Potential of Naturally Occurring Peptides in Counteracting SH-SY5Y Cells Injury

Abstract

Peptides have revealed a large range of biological activities with high selectivity and efficiency for the development of new drugs, including neuroprotective agents. Therefore, this work investigates the neuroprotective properties of naturally occurring peptides, endomorphin-1 (EM-1), endomorphin-2 (EM-2), rubiscolin-5 (R-5), and rubiscolin-6 (R-6). We aimed at answering the question of whether well-known opioid peptides can counteract cell injury in a common in vitro model of Parkinson’s disease (PD). Antioxidant activity of these four peptides was evaluated by the 2-diphenyl-1-picrylhydrazyl radical (DPPH) scavenging activity, oxygen radical absorbance capacity (ORAC), and ferric-reducing antioxidant power (FRAP) assays, while neuroprotective effects were assessed in a neurotoxic model induced by 6-hydroxydopamine (6-OHDA) in a human neuroblastoma cell line (SH-SY5Y). The mechanisms associated with neuroprotection were investigated by the determination of mitochondrial membrane potential (MMP), reactive oxygen species (ROS) production, and Caspase-3 activity. Among the tested peptides, endomorphins significantly prevented neuronal death induced by 6-OHDA treatment, decreasing MMP (EM-1) or Caspase-3 activity (EM-2). Meanwhile, R-6 showed antioxidant potential by FRAP assay and exhibited the highest capacity to recover the neurotoxicity induced by 6-OHDA via attenuation of ROS levels and mitochondrial dysfunction. Generally, we hypothesize that peptides’ ability to suppress the toxic effect induced by 6-OHDA may be mediated by different cellular mechanisms. The protective effect caused by endomorphins results in an antiapoptotic effect (mitochondrial protection and decrease in Caspase-3 activity), while R-6 potency to increase a cell’s viability seems to be mediated by reducing oxidative stress. Our results may provide new insight into neurodegeneration and support the short peptides as a potent drug candidate to treat PD. However, further studies should be conducted on the detailed mechanisms of how tested peptides could suppress neuronal injuries.

Neuroprotective and Anti-inflammatory Effects of Rubiscolin-6 Analogs with Proline Surrogates in Position 2

“…However, when SH-SY5Y cells were treated with 6-OHDA in the presence of peptides (0.1 − 10 µM), R-6 and its four analogs ( 1 , 3 , 5 and 7 ) exhibited the capacity to recover the cell death induced by neurotoxin treatment. Parent peptide increased the cell viability at 20% (at the lowest dose) [ 17 ], while analog 1 at 30% (at the dose of 10 µM), 3 at 15% (at the dose of 1 and 10 µM, respectively), 5 in 14 − 27%, 7 in 22 and 27% (at the dose of 1 and 10 µM, respectively).…”

“…Additionally, our previously published neuroprotective study showed that R-6 possesses neuroprotective potential in the neuroblastoma cells (SH-SY5Y) damage model caused by 6-hydroxydopamine (6-OHDA) treatment [ 17 ]. When SH-SY5Y cells were treated with 6-OHDA (100 µM) in the presence of R-6 (0.1–10 µM) for 24 h, we observed a significant capacity to recover the neurotoxicity induced by neurotoxin treatment.…”

Unlocking the Potential of the Antimicrobial Peptide Gomesin: From Discovery and Structure–Activity Relationships to Therapeutic Applications

“…As a result of resistance, traditional antibiotics are becoming increasingly ineffective, necessitating the development of better antimicrobial alternatives. In addition to existing treatment strategies, such as using conventional antibiotics used to target protein synthesis [ 4 ], antimicrobial peptides (AMPs) are thought to be a feasible alternative for eliminating multidrug-resistant bacteria because their mode of action differs from that of currently available antibiotics; they disturb cell membrane integrity [ 5 , 6 ], impede protein [ 7 , 8 , 9 , 10 , 11 ] and cell wall formation [ 12 , 13 , 14 , 15 ], and alter enzyme function [ 10 , 16 , 17 ]. AMPs can be used for simultaneous or subsequent treatments in many bacterial illnesses as they have independent therapeutic efficacies and fewer adverse effects than conventional antibiotics [ 18 ].…”

Classification of bioactive peptides: a comparative analysis of models and encodings

“…Bioactive peptides (BPs) are short chains of 2 to 50 amino acids with a molecular weight of less than 10 kDa exerting biological effects on unicellular and multicellular organisms [1,2]. Their biological properties make them useful as potential candidates for the treatment of pathologies where conventional medication is ineffective or not advised [3,4]. BPs can have several beneficial functions such as anti-inflammatory, antihypertensive and antidiabetic [1].…”