Lipid Rafts in Trafficking and Processing of Prion Protein and Amyloid Precursor Protein 205

Daniela Sarnataro, Vincenza Campana, and Chiara Zurzolo

10.1 Introduction 205

10.2 Lipid Rafts and Caveolae 206

10.2.1 Biochemical Properties and Functions 206

10.3 PrPc and Prion Diseases 207

10.3.1 The Site of PrPc Conversion: The Role of Rafts in the Different Intracellular Compartments 208

10.3.2 Role of Lipid Rafts in PrPSc Formation 210

10.3.3 Mechanism of Raft Action in Prion Conversion 211

10.3.4 Role of Rafts in Proteolytic Attack on PrPc 214

10.4 Alzheimer's Disease: The Role of Rafts in APP Trafficking and Processing 215

10.4.1 The "History" of APP Cleavage 215

10.4.2 Intracellular Compartments and Ab Generation: Involvement of Lipid Rafts 215

10.4.3 The Role of Rafts in b-Secretase Activity 217

10.4.4 The Role of Caveolae/Lipid Rafts in a-Secretase Activity 220

10.4.4.1 The Role of Lipid Rafts in this Event 221

10.4.5 The Role of Caveolae/Rafts in g-Secretase Activity 221

10.4.6 The Contribution of Cholesterol and Sphingolipids in APP Processing 222

10.5 Conclusions 222

Acknowledgments 223 Abbreviations 223 References 224

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