Whether short peptides are good candidates for future neuroprotective therapeutics?

Perlikowska, Renata

doi:10.1016/j.peptides.2021.170528

Cited by 24 publications

(15 citation statements)

References 188 publications

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“…Till now, several natural or synthetic compounds exert neuroprotective effects by enhancing the expression of BDNF, e.g., citrus flavonoid 3,5,6,7,8,30,40-heptamethoxyflavone (HMF) [ 27 ], or nutraceuticals, such as Phlorotanin extract and β-carotene [ 28 ]. Several studies reported peptides displaying the prosurvival and neuroprotective effects associated with inhibition of oxidative stress, apoptosis, and inflammation [ 5 ]. Among them, there are antioxidant peptides (e.g., Pro-Ala-Tyr-Cys-Ser, Cys-Val-Gly-Ser-Tyr [ 29 ], Dmt-D-Arg-Phe-Lys-NH 2 , Phe-D-Arg-Phe-Lys-NH 2 , and D-Arg-Dmt-Lys-Phe-NH 2 [ 30 , 31 ]), mitochondria-targeted peptides (e.g., cationic-arginine-rich peptides, Penetratin [ 32 ], neuroprotective peptides fused to cell-penetrating peptides [ 33 , 34 ]), endogenous peptides (e.g., Apelin-family peptides [ 35 ] and Humanin [ 36 ]), opioid peptides (e.g., mentioned above endomorphins [ 12 , 13 , 14 , 15 , 16 ] and Tyr-D-Ala-Gly-MePhe-Gly-ol [ 37 ]), and many others (see more in Ref.…”

Section: Discussionmentioning

confidence: 99%

“…The research results so far confirm that opioid peptides promote the survival of neurons during the development of the nervous system, influencing their proliferation and migration [ 5 ]. Endomorphins were considered cytoprotective and prosurvival agents; they scavenged radicals, inhibited lipid peroxidation, DNA, and protein oxidative damage [ 12 ], as well as prevented oxidative damage of LDL in in vitro injury models generated by 2,2′-azobis (2-amidinopropane hydrochloride) (AAPH), H 2 O 2 , or copper ions [ 13 ].…”

Section: Introductionmentioning

confidence: 86%

“…According to evidence, the human neuroblastoma cell line (SH-SY5Y) selected in this study shares some morphological, neurochemical, and electrophysiological properties with normal neurons and is characterized by its low differentiation, pyramidal shape, and obvious axon. The SH-SY5Y cells have been extensively used as a model to study the neurotoxicity of numerous stimulants in vitro [ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

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

Perlikowska

Silva

Alves

et al. 2022

IJMS

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 86%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Perlikowska

Silva

Alves

et al. 2022

IJMS

Self Cite

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“…Val and Leu were only found in RPVLGGSSTFPYP. The hydrophobicity of peptides enabled their penetration into the cells to reach and act on their specific targets, as well as increasing the solubility of the peptides in lipids facilitated in contact with hydrophobic radical species (Vo, Ryu & Kim, 2013;Perlikowska, 2021). Furthermore, basic amino acids found in 50% of the neuroprotective peptides also contributed to neuroprotective functions (Wang, Waterhouse, Waterhouse, Zheng, Su, & Zhao, 2021).…”

Section: Discussionmentioning

confidence: 99%

“…There is a growing interest in the use of food-derived bioactive products as intervention agents in functional foods and dietary supplements for the fights against these human diseases (Wang, Waterhouse, Waterhouse, Zheng, Su, & Zhao, 2021). Among many classes of compounds considers as neuroprotective agents, peptides derived from natural materials or their synthetic analogs are good candidates (Perlikowska, 2021).…”

Section: Introductionmentioning

confidence: 99%

Novel neuroprotective peptides derived from enzymatic hydrolysis of pea protein

Chiang

Hsu

2022

Preprint

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The aim of this study was to purify and identify neuroprotective peptides derived from Flavourzyme ® -pea protein hydrolysate (FPPH). Cell viability of β-amyloid peptide (Aβ 1−42 )-induced oxidative damage in SH-SY5Y cells was used to explore neuroprotective effects of pretreating the cells with or without hydrolysate and its fractions. The higher cell viability represents the better neuroprotective effect. The hydrolysate was sequentially purified by gel filtration (GF) chromatography, reversed-phase (RP) chromatography and cation-exchange (CE) chromatography to explore any fraction to increase neuroprotective effects. The peptides were identified using a liquid chromatography tandem mass spectrometer (LC/MS/MS). Three novel neuroprotective peptides were obtained, and the amino acid sequences were NKFGKFF, GGPFKSPF and RPVLGGSSTFPYP. The in vitro effect of gastrointestinal proteases on neuroprotective effects of the three peptides were 23 also investigated. The result suggested that the gastrointestinal protease did 24 not affect neuroprotective effects of the three novel peptides, which reveal the 25 potential to ameliorate disease caused by neurodegeneration.

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

Perlikowska,

Silva,

Alves

et al. 2023

Neurochem Res

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Naturally occurring peptides, such as rubiscolins derived from spinach leaves, have been shown to possess some interesting activities. They exerted central effects, such as antinociception, memory consolidation and anxiolytic-like activity. The fact that rubiscolins are potent even when given orally makes them very promising drug candidates. The present work tested whether rubiscolin-6 (R-6, Tyr-Pro-Leu-Asp-Leu-Phe) analogs have neuroprotective and anti-inflammatory effects. These hypotheses were tested in the 6-hydroxydopamine (6-OHDA) injury model of human neuroblastoma SH-SY5Y and lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. The determination of reactive oxygen species (ROS), mitochondrial membrane potential (MMP), Caspase-3 activity, lipid peroxidation and nitric oxide (NO) production allowed us to determine the effects of peptides on hallmarks related to Parkinson’s Disease (PD) and inflammation. Additionally, we investigated the impact of R-6 analogs on serine-threonine kinase (also known as protein kinase B, AKT) and mammalian target of rapamycin (mTOR) activation. The treatment with analogs 3 (Tyr-Inp-Leu-Asp-Leu-Phe-OH), 5 (Dmt-Inp-Leu-Asp-Leu-Phe-OH) and 7 (Tyr-Inp-Leu-Asp-Leu-Phe-NH2) most effectively prevented neuronal death via attenuation of ROS, mitochondrial dysfunction and Caspase-3 activity. Peptides 5 and 7 significantly increased the protein expression of the phosphorylated-AKT (p-AKT) and phosphorylated-mTOR (p-mTOR). Additionally, selected analogs could also ameliorate LPS-mediated inflammation in macrophages via inhibition of intracellular generation of ROS and NO production. Our findings suggest that R-6 analogs exert protective effects, possibly related to an anti-oxidation mechanism in in vitro model of PD. The data shows that the most potent peptides can inhibit 6-OHDA injury by activating the PI3-K/AKT/mTOR pathway, thus playing a neuroprotective role and may provide a rational and robust approach in the design of new therapeutics or even functional foods.

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Whether short peptides are good candidates for future neuroprotective therapeutics?

Cited by 24 publications

References 188 publications

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

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

Novel neuroprotective peptides derived from enzymatic hydrolysis of pea protein

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

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