Molecular Targets in Protein Misfolding and Neurodegenerative Disease

Molecular Targets in Protein Misfolding and Neurodegenerative Disease

1st Edition - October 7, 2014

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  • Author: Pierfausto Seneci
  • eBook ISBN: 9780128004999
  • Hardcover ISBN: 9780128001868

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Aimed at "drug discoverers" – i.e. any scientist who is interested in neurodegenerative diseases in general, and in finding disease-modifying treatments in particular – the first edition of Molecular Targets in Protein Misfolding and Neurodegenerative Disease will contain both a detailed, discipline-specific coverage (paragraphs on medicinal chemistry, on clinical and preclinical characterization of compounds in development, on target identification and validation, on genetic factors influencing a pathology, etc.) and a drug discovery-oriented, overall evaluation of each target (validation, druggability, existing leads, etc.). Together these will satisfy the needs of various audiences, including in vitro biologists, pharmacologists, medicinal chemists, etc.

Key Features

  • Written to provide a comprehensive coverage of disease-modifying mechanisms and compounds against neurodegenerative diseases
  • Provides a “drug discovery” application oriented perspective, evaluating targets and candidates for their overall therapeutic potential
  • Provides discipline-specific chapters (medicinal chemistry, target validation, preclinical and clinical development
  • Provides an overview on a number of molecular mechanisms (e.g. phosphorylation, chaperon refolding, ubiquitination, autophagy, microtubule transportation, protease cleavage, etc.) with relevance for any disease area
  • Contains a more thorough description of the therapeutic relevance of ~10 specific molecular targets


Graduate students in neuroscience, broader biological sciences, medicinal chemists, post-doctoral fellows, and drug discovery/ preclinical researchers

Table of Contents

  • Chapter 1: Protein Misfolding, Neurodegeneration and Tau

    • Abstract
    • 1.1. The neurodegeneration scenario
    • 1.2. Protein folding: physiological benefits and pathological consequences
    • 1.3. Tau: an intrinsically disordered, flexible, and aggregation-prone protein
    • 1.4. Tauopathies: aggregation-prone tau in neurodegenerative disease (NDD)

    Chapter 2: Targeting the Protein Quality Control (PQC) Machinery

    • Abstract
    • 2.1. Molecular chaperones, PQC, and neurodegeneration
    • 2.2. Molecular targets
    • 2.3. Disease-modifying compounds

    Chapter 3: Proteasomal Degradation of Soluble, Misfolded Proteins

    • Abstract
    • 3.1. UPS-mediated degradation of misfolded proteins
    • 3.2. UPS-mediated degradation of misfolded proteins in NDDs
    • 3.3. UPS—targets
    • 3.4. Disease-modifying compounds

    Chapter 4: Unselective Disposal of Cellular Aggregates

    • Abstract
    • 4.1. Autophagy-mediated degradation of protein aggregates
    • 4.2. Autophagy-mediated degradation of protein aggregates in NDDs
    • 4.3. Macroautophagy—targets
    • 4.4. Disease-modifying compounds

    Chapter 5: Selective Disposal of Insoluble Protein Aggregates

    • Abstract
    • 5.1. Aggrephagy-mediated degradation of protein aggregates
    • 5.2. Selective autophagy-mediated degradation of protein aggregates in NDDs
    • 5.3. Selective autophagy—targets
    • 5.4. Disease-modifying compounds

    Chapter 6: Assembly and Disassembly of Protein Aggregates

    • Abstract
    • 6.1. Introduction
    • 6.2. Disordered protein aggregates and ordered amyloid fibrils
    • 6.3. Chaperone-driven disaggregation of protein aggregates
    • 6.4. Disease-modifying compounds

Product details

  • No. of pages: 314
  • Language: English
  • Copyright: © Academic Press 2014
  • Published: October 7, 2014
  • Imprint: Academic Press
  • eBook ISBN: 9780128004999
  • Hardcover ISBN: 9780128001868

About the Author

Pierfausto Seneci

Dr. Pierfausto Seneci is Associate Professor in the Department of Organic and Industrial Chemistry at the University of Milan. He is currently affiliated with the University of Milan Centre for Interdisciplinary Biomolecular Studies and Industrial Applications (CISI) Centre of Excellence, and is responsible for the Combinatorial Chemistry/High Throughput MedChem Laboratory. He has over 20 years of medicinal chemistry experience working in industry, and held business development positions with GSK, Sanofi, and start-up pharmaceutical companies including Sirenade and NiKem working in drug discovery, neurodegeneration, oncology, and antibacterials. He is author of approximately 80 papers on the topic and several book chapters, including the book “Solid-Phase Synthesis and Combinatorial Technologies” with Wiley-Interscience in 2000.

Affiliations and Expertise

Associate Professor, Department of Organic and Industrial Chemistry, University of Milan, Milan, Italy

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