Heat Shock Proteins of Malaria

Preface
Acknowledgments
Contents
Editors and Contributors
Chapter 1: Introductory Chapter: The Importance of Heat Shock Proteins in Survival and Pathogenesis of the Malaria Parasite Pl...
	1.1 Introduction
	1.2 Parasites are Highly Dependent on HSPs
	1.3 At Home: Cytosolic Plasmodium HSPs
	1.4 Into the Wild: Plasmodium HSPs Involved in Interaction with the Host
	1.5 Achilles´ Molecular Heel: HSPs as a Target for Drug Development
	1.6 Concluding Comments
	References
Chapter 2: General Structural and Functional Features of Molecular Chaperones
	2.1 Introduction to Molecular Chaperones and Stress at a Cellular Level
	2.2 Classification of Heat Shock Proteins as Molecular Chaperones
	2.3 Foldases: Molecular Chaperones Involved in Protein Folding
		2.3.1 The Hsp60/Chaperonin Family of Molecular Chaperones
		2.3.2 The Hsp90 Family of Molecular Chaperones
		2.3.3 The Hsp70 and Hsp110 Family of Molecular Chaperones
		2.3.4 The JDP Family of Molecular Chaperones
	2.4 Holdases and Unfoldases: Molecular Chaperones Preventing Protein Aggregation and Promoting Disaggregation or Degradation
		2.4.1 The Small Heat Shock Protein Family (sHsp)
		2.4.2 The Hsp100/Clp Family of Molecular Chaperones
	2.5 Heat Shock Proteins are Essential for the Survival of Plasmodium falciparum
	References
Chapter 3: The Role of Hsp70s in the Development and Pathogenicity of Plasmodium falciparum
	3.1 Introduction
	3.2 The Role of Plasmodial Heat Shock Proteins at the Host-Parasite Interface
	3.3 The Structural and Functional Features of Hsp70
	3.4 Hsp70s from P. falciparum
	3.5 Cytosol Localised Hsp70s
		3.5.1 PfHsp70-1
		3.5.2 PfHsp70-z
	3.6 Endoplasmic Reticulum Hsp70s
		3.6.1 PfHsp70-2
		3.6.2 PfHsp70-y
		3.6.3 Mitochondrial Hsp70
	3.7 Exported Hsp70
		3.7.1 The Role of Parasite Heat Shock Proteins in Host Cell Remodelling
		3.7.2 PfHsp70-x
	3.8 Conclusion
	References
Chapter 4: Role of the J Domain Protein Family in the Survival and Pathogenesis of Plasmodium falciparum
	4.1 Introduction
		4.1.1 Structural and Functional Features of PfJDPs
		4.1.2 Implications of the Expanded PfJDP Arsenal
		4.1.3 Localisation and Expression of PfJDPs in the Malaria Parasite
	4.2 Parasite-Resident PfJDPs
		4.2.1 PF14_0359
		4.2.2 Pfj1
		4.2.3 Pfj2
		4.2.4 Pfj4
		4.2.5 PFB0595w
	4.3 Exported PfJDPs
		4.3.1 Protein Export
		4.3.2 Exported Type II PfJDPs and J-Dots
		4.3.3 Exported Type III PfJDPs
		4.3.4 Exported Type IV PfJDPs
	4.4 PfJDPs as Potential Drug Targets
	4.5 Conclusion
	References
Chapter 5: Role of Hsp90 in Plasmodium falciparum Malaria
	5.1 Heat Shock Protein 90: A Potentiator for Pathogen Acclimatization
	5.2 PfHsp90: Biochemical Characterization
	5.3 The Role of PfHsp90 in the Cell: Heat Shock and Stage Transition
	5.4 The Role of Host Hsp90 in P. falciparum Infection
	5.5 Conclusion
	References
Chapter 6: The Role of Malaria Parasite Heat Shock Proteins in Protein Trafficking and Remodelling of Red Blood Cells
	6.1 Introduction
	6.2 The Role of Heat Shock Proteins in the Protein Export Pathway
		6.2.1 Endoplasmic Reticulum: A Sorting Nexus for Many Destinations
			6.2.1.1 Import of Proteins into the ER
			6.2.1.2 Protein Quality Control
			6.2.1.3 Delivery of Proteins to the Parasitophorous Vacuole That Are Destined for Export
		6.2.2 Protein Translocation Across the Parasitophorous Vacuole Membrane
			6.2.2.1 Molecular Mechanism of HSP101 Function
			6.2.2.2 HSP101 Co-chaperones
	6.3 The Role of Heat Shock Proteins in Orchestrating Host Cell Renovation
		6.3.1 Exported JDPs/HSP70-x
		6.3.2 Host Cell Modifications by Heat Shock Proteins
			6.3.2.1 Membranous Network and Trafficking Highways Within the Host Cell
			6.3.2.2 Erythrocyte Deformability
			6.3.2.3 Recruitment of Host Chaperones
	6.4 The Role of Heat Shock Chaperones in the Import of Proteins into Organelles of Endosymbiotic Origin
		6.4.1 The Contribution of Heat Shock Proteins in Protein Trafficking into the Apicoplast
		6.4.2 Import of Mitochondrial Proteins
			6.4.2.1 Insertion of Carrier Proteins into the Inner Membrane of Mitochondria
			6.4.2.2 Import of Proteins into the Matrix of Mitochondria
	6.5 Conclusions
	References
Chapter 7: Role of Heat Shock Proteins in Immune Modulation in Malaria
	7.1 Introduction
	7.2 Parasite Heat Shock Proteins
	7.3 Host Heat Shock Proteins
	7.4 Future Perspectives with Respect to New Treatment Strategies for Malaria
	References
Chapter 8: Bioprospecting for Novel Heat Shock Protein Modulators: The New Frontier for Antimalarial Drug Discovery?
	8.1 Antimalarial Drug Resistance
	8.2 Heat Shock Proteins as Potential Antimalarial Drug Targets
	8.3 Structure-Function Features of Hsps That Make Them Amenable to Inhibitor Screening
	8.4 Plants as Sources of Antimalarial Chemotherapeutic Agents
	8.5 Natural Compounds Targeting Hsps and Their Prospects as Antimalarials
		8.5.1 Phenolics
			8.5.1.1 Chalcones
		8.5.2 Polyphenols
		8.5.3 Terpenoids
		8.5.4 Alkaloids
		8.5.5 Cyclic Peptides
		8.5.6 Other Compounds
	8.6 Various Plant Derived Polyphenols Show Common Inhibitory Mechanisms
	8.7 Challenges and Opportunities of Identifying and Designing Antimalarial Compounds from Natural Sources
	References
Chapter 9: Heat Shock Proteins as Targets for Novel Antimalarial Drug Discovery
	9.1 Introduction
		9.1.1 The Burden of Malaria and Global Efforts in Its Eradication
		9.1.2 Challenges Posed by the Parasite
		9.1.3 Targeting HSPs as a Potential Solution
	9.2 Features of HSPs That Can Be Exploited in Antimalarial Drug Discovery
		9.2.1 Features of Plasmodial Hsp90
		9.2.2 Features of Plasmodial Hsp70
		9.2.3 Features in Plasmodial Hsp40s
		9.2.4 Features of Plasmodial Hsp60 and Small HSP (sHSP)
		9.2.5 Functional Interactions as Features for Drug Targeting
	9.3 Screening Strategies for the Discovery of Small Molecule Inhibitors of Chaperones
		9.3.1 Introduction
		9.3.2 Targeting Plasmodial Hsp90 Functional Activities
		9.3.3 Targeting Hsp70 Functional Activities
		9.3.4 Targeting Hsp40 Functional Activities
		9.3.5 Targeting HSPs Functional Interactions
	9.4 Application of HSPs in High Throughput Antimalarial Drug Screening
	9.5 Application of HSPs in Computer-Aided Drug Design (CAAD) and Screening
	9.6 Conclusion
	References
Chapter 10: Heat Shock Proteins of Malaria: Highlights and Future Prospects
	References
Index