Caspase-1 and Cathepsin B Inhibitors from Marine Invertebrates, Aiming at a Reduction in Neuroinflammation

Area of Science:

• Marine Biology
• Neuroscience
• Biochemistry

Background:

• Neuroinflammation, driven by amyloid peptides and microglial activation, is central to dementia, including Alzheimer's disease (AD).
• Key enzymes like caspase-1 and cathepsin B mediate neuroinflammation in AD, making them therapeutic targets.
• Identifying novel modulators of these enzymes offers a promising strategy for treating neurodegenerative diseases.

Purpose of the Study:

• To discover new inhibitors of caspase-1 and cathepsin B from Brazilian marine invertebrates.
• To identify and characterize the specific molecules responsible for enzyme inhibition.

Main Methods:

• Screening of extracts from five Brazilian marine invertebrate species (four cnidarians, one echinoderm) for enzyme inhibitory activity.
• Fractionation of active extracts and purification of inhibitory compounds.
• Identification of purified molecules using mass spectrometry.

Main Results:

• The extract of *Chiropsalmus quadrumanus* (box jellyfish) inhibited caspase-1, yielding the identified molecule trigonelline.
• Four extracts inhibited cathepsin B; fractionation of *Exaiptasia diaphana* led to the identification of betaine.
• This study is the first to demonstrate potent inhibitory effects of these compounds on caspase-1 and cathepsin B.

Conclusions:

• Trigonelline and betaine, isolated from marine invertebrates, are potent inhibitors of caspase-1 and cathepsin B, respectively.
• These identified molecules represent new prototypes for enzyme inhibition and potential therapeutic agents for neuroinflammation.
• Further development of these compounds could lead to novel treatments for neurodegenerative diseases like Alzheimer's.