Seneci Molecular Targets in Protein Misfolding and Neurodegenerative Disease

1. Auflage 2014
ISBN: 978-0-12-800499-9
Verlag: William Andrew Publishing
Format: EPUB
Kopierschutz: 6 - ePub Watermark

E-Book, Englisch, 314 Seiten, Format (B × H): 152 mm x 229 mm

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. - 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

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.

Autoren/Hrsg.

Seneci, Pierfausto

Fachgebiete

• Medizin | Veterinärmedizin Medizin | Public Health | Pharmazie | Zahnmedizin Pharmazie
• Medizin | Veterinärmedizin Medizin | Public Health | Pharmazie | Zahnmedizin Klinische und Innere Medizin Neurologie, Klinische Neurowissenschaft
• Medizin | Veterinärmedizin Medizin | Public Health | Pharmazie | Zahnmedizin Medizinische Fachgebiete Pharmakologie, Toxikologie
• Interdisziplinäres Wissenschaften Wissenschaften Interdisziplinär Neurowissenschaften, Kognitionswissenschaft

Inhaltsverzeichnis

Chapter 1 - Protein misfolding, neurodegeneration and Tau: The main players, or the usual suspects? Chapter 2 - Targeting the protein quality control (PQC) machinery: The neuronal Salvation Army. Chapter 3 - Proteasomal degradation of soluble, misfolded proteins: Throwing out the bath water, but where's the baby? Chapter 4 - Unselective disposal of cellular aggregates: Engulf, devour and digest to recycle. Chapter 5 - Selective disposal of insoluble protein aggregates: Pick, transport and remove to cure. Chapter 6 - Assembly and disassembly of protein aggregates: Unraveling the maze. Conclusion

Leseproben

Abbreviations
4EBP1    4E-binding protein 1 AA    amino acid AAA+    ATPases associated with various cellular activities Aß    amyloid ß ABIN    A20 binding inhibitor of NF-kappaB ACD    a-crystallin domain AChE    acetylcholinesterase AD    Alzheimer’s disease ADI    Alzheimer’s disease international Adrm1    adhesion regulating molecule 1 AFM    atomic force microscopy Ag    aggregate AgD    argyrophilic disease AgR    aggrephagy receptor AgS    aggrephagy scaffold Aha1    activator of Hsp90 ATPase AIM    Atg8-interacting motif Akt    protein kinase B ALFY    autophagy linked FYVE protein ALR    autophagic lysosomal reformation ALS    amyotrophic lateral sclerosis AMBRA1    autophagy/beclin 1 regulator 1 AmF    amyloid fiber AMPA    a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid AMPK    AMP-activated protein kinase AN    aggregation nuclei AMSH-LP    associated molecule with the SH3 domain of STAM-like protein AP    autophagosomes APD    atypical parkinsonism disorder APOE    apolipoprotein E APP    amyloid precursor protein ARA54    AR-associated protein 54 ARCA    autosomal recessive cerebellar ataxia ARIH    ariadne homolog Atg    autophagy-related AV    autophagic vacuoles BACE1    ß-APP cleaving enzyme 1 BAG    Bcl-2-associated athanogene BARD1    BRCA1–associated RING domain protein 1 Barkor    beclin 1-associated autophagy-related key regulator BDNF    brain-derived neurotrophic factor BEACH    PH-Beige and Chediak-Higashi BH    Bcl-2-homology BIF-1    BAX-interacting factor-1 Bnip-3    Bcl-2/E1B-19 kDa interacting protein 3 BRCA1    breast cancer type 1 BRMS1    breast cancer metastasis suppressor 1 CA1    cornus ammonis 1 Car    cargo CASA    chaperone-assisted selective autophagy Cath A    cathepsin A CBD    corticobasal degeneration CD4    cluster of differentiation 4 cdc37    cell division cycle 37 homolog Cdk    cyclin-dependent kinase CFTR    cystic fibrosis transmembrane regulator Ch    cholesterol CHIP    C-terminus of Hsc70 interacting protein CHMPB2    charged multivesicular body protein B2 cIAP    cellular Inhibitor of Apoptosis Protein CK2    casein kinase 2 Clp    caseinolytic protease CMA    chaperone-mediated autophagy CMT    Charcot–Marie–Tooth disease CNS    central nervous system CP    core particle CRL    cullin RING ligases CTE    chronic traumatic encephalopathy Cvt    cytosol-to-vacuole transport CYLD    cylindromatosis Cyp40/Cpr6    cyclophilin 40/cytoplasmic ribosomal protein-6 Cyt    cytosolic D    dimer DA    disordered aggregate DAP1    death-associated protein 1 DAPK    death-associated protein kinase dAV    degradative autophagic vacuoles DBM    dynein binding motor Ddi1    DNA damage-inducible 1 DHMN    distal hereditary motor neuropathy DLB    dementia with Lewy bodies DLS    dynamic light scattering DM1    type I myotonic dystrophy DNTC    diffuse neurofibrillary tangles with calcification DRAM    damage-regulated autophagy modulator DS    Down syndrome Dsk2    dominant suppressor of kar2 DUB    de-ubiquitinating enzyme DYN    dynein motors E1    UBQ-activating enzyme E2    UBQ-conjugating enzyme E3    UBQ ligase E6AP    E6-associated protein EC    entorhinal cortex ECD    evolutionary conserved domain eIF4E    eukaryotic translation initiation factor 4 epsilon EM    electron microscopy ER    endoplasmic reticulum ERAD    endoplasmic reticulum-associated degradation ERGIC    ER-Golgi intermediate compartment ERK    extracellular-regulated signal kinase ES    endosomes ESCRT    endosomal sorting complex required for transport machinery ESI    electron spray ionization FAT    fast axonal transport FATC    FRAP, ATM, TRRAP C-terminal FBD    familial British dementia FDD    familial Danish dementia FIP200    focal adhesion kinase family-interacting protein FKBP    FK-binding protein FL    full length FRB    FKBP–rapamycin binding FTDP-17    frontotemporal dementia and parkinsonism linked to chromosome 17 FTLD    frontotemporal lobar degeneration FUS    fused in sarcoma FYCO    FYVE and coiled-coil domain containing 1 FYVE    Fab1-YotB-Vac1p-EEA1 G2E3    G2/M-phase-specific E3 UBQ ligase G3BP1    Ras-GTPase-activating protein SH3 domain-binding protein 1 GABA    ?-aminobutyric acid GABARAP    GABA receptor-associated proteins Gad    gracile axonal dystrophy Gd-PDG    Guadeloupean-parkinsonism dementia complex GGT    globular glial tauopathies GOF    gain-of-function GR    glucocorticoid receptor GSK-3    glycogen synthase kinase 3 GSS    Gerstmann–Sträussler–Scheinker disease H    heparin HACEI1    HECT domain and ankyrin repeat-containing E3 ubiquitin-protein ligase...