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Mar Drugs
2022 Sep 23;2010:. doi: 10.3390/md20100614.
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Caspase-1 and Cathepsin B Inhibitors from Marine Invertebrates, Aiming at a Reduction in Neuroinflammation.
Moreno RI
,
Zambelli VO
,
Picolo G
,
Cury Y
,
Morandini AC
,
Marques AC
,
Sciani JM
.
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Neuroinflammation is a condition associated with several types of dementia, such as Alzheimer's disease (AD), mainly caused by an inflammatory response to amyloid peptides that induce microglial activation, with subsequent cytokine release. Neuronal caspase-1 from inflammasome and cathepsin B are key enzymes mediating neuroinflammation in AD, therefore, revealing new molecules to modulate these enzymes may be an interesting approach to treat neurodegenerative diseases. In this study, we searched for new caspase-1 and cathepsin B inhibitors from five species of Brazilian marine invertebrates (four cnidarians and one echinoderm). The results show that the extract of the box jellyfish Chiropsalmus quadrumanus inhibits caspase-1. This extract was fractionated, and the products monitored for their inhibitory activity, until the obtention of a pure molecule, which was identified as trigonelline by mass spectrometry. Moreover, four extracts inhibit cathepsin B, and Exaiptasia diaphana was selected for subsequent fractionation and characterization, resulting in the identification of betaine as being responsible for the inhibitory action. Both molecules are already found in marine organisms, however, this is the first study showing a potent inhibitory effect on caspase-1 and cathepsin B activities. Therefore, these new prototypes can be considered for the enzyme inhibition and subsequent control of the neuroinflammation.
ACKERMANN,
The occurrence of homarine, trigonelline and an new anemonine base in the Anthozoan Anemonia sulcata.
1953, Pubmed
ACKERMANN,
The occurrence of homarine, trigonelline and an new anemonine base in the Anthozoan Anemonia sulcata.
1953,
Pubmed
Arruda,
Box Jellyfish (Cnidaria, Cubozoa) Extract Increases Neuron's Connection: A Possible Neuroprotector Effect.
2021,
Pubmed
Assfalg-Machleidt,
Cathepsin B-indicator for the release of lysosomal cysteine proteinases in severe trauma and inflammation.
1990,
Pubmed
Brix,
Cysteine cathepsins: cellular roadmap to different functions.
2008,
Pubmed
Campden,
The role of lysosomal cysteine cathepsins in NLRP3 inflammasome activation.
2019,
Pubmed
Carrillo-Mora,
Amyloid beta: multiple mechanisms of toxicity and only some protective effects?
2014,
Pubmed
Cataldo,
Enzymatically active lysosomal proteases are associated with amyloid deposits in Alzheimer brain.
1990,
Pubmed
Chevriaux,
Cathepsin B Is Required for NLRP3 Inflammasome Activation in Macrophages, Through NLRP3 Interaction.
2020,
Pubmed
Davalos,
ATP mediates rapid microglial response to local brain injury in vivo.
2005,
Pubmed
Davis,
The inflammasome NLRs in immunity, inflammation, and associated diseases.
2011,
Pubmed
DiSabato,
Neuroinflammation: the devil is in the details.
2016,
Pubmed
Flores,
Caspase-1 inhibition alleviates cognitive impairment and neuropathology in an Alzheimer's disease mouse model.
2018,
Pubmed
Freeman,
The pathogenic role of the inflammasome in neurodegenerative diseases.
2016,
Pubmed
Gan,
Identification of cathepsin B as a mediator of neuronal death induced by Abeta-activated microglial cells using a functional genomics approach.
2004,
Pubmed
Grabowska,
Association constants of pyridine and piperidine alkaloids to amyloid beta peptide determined by electrochemical impedance spectroscopy.
2010,
Pubmed
Grajales,
Morphological revision of the genus Aiptasia and the family Aiptasiidae (Cnidaria, Actiniaria, Metridioidea).
2014,
Pubmed
Halle,
The NALP3 inflammasome is involved in the innate immune response to amyloid-beta.
2008,
Pubmed
Hanslik,
The Role of Microglia and the Nlrp3 Inflammasome in Alzheimer's Disease.
2020,
Pubmed
Heneka,
NLRP3 is activated in Alzheimer's disease and contributes to pathology in APP/PS1 mice.
2013,
Pubmed
Hentze,
Critical role for cathepsin B in mediating caspase-1-dependent interleukin-18 maturation and caspase-1-independent necrosis triggered by the microbial toxin nigericin.
2003,
Pubmed
Hook,
Inhibition of cathepsin B reduces beta-amyloid production in regulated secretory vesicles of neuronal chromaffin cells: evidence for cathepsin B as a candidate beta-secretase of Alzheimer's disease.
2005,
Pubmed
Hook,
Brain pyroglutamate amyloid-β is produced by cathepsin B and is reduced by the cysteine protease inhibitor E64d, representing a potential Alzheimer's disease therapeutic.
2014,
Pubmed
Hook,
Cathepsin B in neurodegeneration of Alzheimer's disease, traumatic brain injury, and related brain disorders.
2020,
Pubmed
Hook,
Inhibitors of cathepsin B improve memory and reduce beta-amyloid in transgenic Alzheimer disease mice expressing the wild-type, but not the Swedish mutant, beta-secretase site of the amyloid precursor protein.
2008,
Pubmed
Jaimes-Becerra,
Comparative proteomics reveals recruitment patterns of some protein families in the venoms of Cnidaria.
2017,
Pubmed
Kindy,
Deletion of the cathepsin B gene improves memory deficits in a transgenic ALZHeimer's disease mouse model expressing AβPP containing the wild-type β-secretase site sequence.
2012,
Pubmed
Liu,
Trigonelline inhibits caspase 3 to protect β cells apoptosis in streptozotocin-induced type 1 diabetic mice.
2018,
Pubmed
McGlinchey,
Cysteine cathepsins are essential in lysosomal degradation of α-synuclein.
2015,
Pubmed
McKenzie,
Caspase-1 inhibition prevents glial inflammasome activation and pyroptosis in models of multiple sclerosis.
2018,
Pubmed
Mueller-Steiner,
Antiamyloidogenic and neuroprotective functions of cathepsin B: implications for Alzheimer's disease.
2006,
Pubmed
Murata,
Novel epoxysuccinyl peptides. Selective inhibitors of cathepsin B, in vitro.
1991,
Pubmed
Murayama,
Shishicrellastatins, inhibitors of cathepsin B, from the marine sponge Crella (Yvesia) spinulata.
2011,
Pubmed
Paldino,
Emerging Role of NLRP3 Inflammasome/Pyroptosis in Huntington's Disease.
2022,
Pubmed
Pfeifer,
Control of formation of the two types of polyps in Thecocodium quadratum (Hydrozoa, Cnidaria).
1995,
Pubmed
Pike,
The potential convergence of NLRP3 inflammasome, potassium, and dopamine mechanisms in Parkinson's disease.
2022,
Pubmed
Pišlar,
Cysteine cathepsins in neurological disorders.
2014,
Pubmed
Poulin,
Chemical encoding of risk perception and predator detection among estuarine invertebrates.
2018,
Pubmed
Ramos,
Palytoxin and analogs: biological and ecological effects.
2010,
Pubmed
Sciani,
Initial peptidomic profiling of Brazilian sea urchins: Arbacia lixula, Lytechinus variegatus and Echinometra lucunter.
2016,
Pubmed
,
Echinobase
Sciani,
Cathepsin B/X is secreted by Echinometra lucunter sea urchin spines, a structure rich in granular cells and toxins.
2013,
Pubmed
,
Echinobase
Sun,
Translational study of Alzheimer's disease (AD) biomarkers from brain tissues in AβPP/PS1 mice and serum of AD patients.
2015,
Pubmed
Sundelöf,
Higher cathepsin B levels in plasma in Alzheimer's disease compared to healthy controls.
2010,
Pubmed
Taneo,
Amyloid β oligomers induce interleukin-1β production in primary microglia in a cathepsin B- and reactive oxygen species-dependent manner.
2015,
Pubmed
Tian,
Sevoflurane Aggravates the Progress of Alzheimer's Disease Through NLRP3/Caspase-1/Gasdermin D Pathway.
2021,
Pubmed
Tohda,
Search for natural products related to regeneration of the neuronal network.
2005,
Pubmed
Williams,
The global diversity of sea pens (Cnidaria: Octocorallia: Pennatulacea).
2011,
Pubmed
Yajun,
Betaine Attenuates Osteoarthritis by Inhibiting Osteoclastogenesis and Angiogenesis in Subchondral Bone.
2021,
Pubmed
Yan,
Molecular regulation of human cathepsin B: implication in pathologies.
2003,
Pubmed
Yancey,
Betaines and dimethylsulfoniopropionate as major osmolytes in cnidaria with endosymbiotic dinoflagellates.
2010,
Pubmed
Zhang,
NLRP3 inflammasome as a novel therapeutic target for Alzheimer's disease.
2020,
Pubmed
Zhou,
Thioredoxin-interacting protein links oxidative stress to inflammasome activation.
2010,
Pubmed
Zhukovskiĭ,
[Inhibition of cholinesterases of varying origin by ordinary and betaine vinylphosphates].
1996,
Pubmed