Update on relevant trypanosome peptidases: Validated targets and future challenges.

Area of Science:

• Parasitology
• Biochemistry
• Drug Discovery

Background:

• Trypanosoma cruzi causes Chagas disease, while Trypanosoma brucei gambiense and T. brucei rhodesiense cause Human African Trypanosomiasis (HAT).
• These parasites possess various peptidases, including abundant cysteine proteases like cruzipain and rhodesain, vital for their survival.
• These essential enzymes represent potential therapeutic targets for treating these neglected diseases.

Purpose of the Study:

• To review the role of peptidases in Trypanosoma parasites.
• To highlight proteases as drug targets for Chagas disease and HAT.
• To discuss recent advancements in developing selective protease inhibitors.

Main Methods:

• Literature review of characterized peptidases in Trypanosoma species.
• Analysis of the abundance and essentiality of specific protease families.
• Evaluation of recent findings on parasite-selective proteasome inhibitors.

Main Results:

• Cysteine proteases (Clan CA), including Cathepsin L-like cruzipain and rhodesain, and Cathepsin B-like enzymes, are abundant and crucial in T. cruzi and T. brucei.
• Several other characterized proteases also show potential as drug candidates.
• Novel inhibitors with high selectivity for parasite proteasomes have been identified.

Conclusions:

• Proteases are essential for Trypanosoma parasites, making them viable targets for chemotherapy.
• Targeted inhibitors, particularly those acting on parasite proteasomes, represent promising lead compounds for new drug development against neglected trypanosomiases.