Molecular targets in protein misfolding and neurodegenerative disease / Pierfausto Seneci.

Format:

Book

Author/Creator:

Seneci, Pierfausto, 1960- author.

Contributor:

ebrary, Inc.

Gail and Warren Lieberfarb Mental Health and Neuroscience Library Resources Fund.

Language:

English

Subjects (All):

Nervous system--Degeneration.

Nervous system.

Neurodegenerative Diseases.

Medical Subjects:

Neurodegenerative Diseases.

Physical Description:

1 online resource (xvii, 295 pages.)

Place of Publication:

London, UK : Academic Press/Elsevier, [2015]

System Details:

text file

Summary:

Molecular Targets in Protein Misfolding and Neurodegenerative Disease is a multi-disciplinary portrayal of CNS proteinopathies focusing on putative disease-modifying approaches and molecular targets. The therapeutic targets of focus here are Tau-dependent tauopathies, and the five known pathologically impaired pathways of chaperone refolding, the ubiquitin-proteasome system, macro-autophagy, aggrephagy, and protein aggregation as a biophysical chain of events are thoroughly described. Therapeutic intervention data by way of discovery, preclinical, and clinical validation are also presented for nine promising disease-modifying molecular targets-Hsp27, Hsp70, Hsp90, CHIP, USP14, mTORC1, p62, HDAC6, and the aggregation process of tau. The volume provides an integrated, R&D-oriented overview of protein misfolding diseases and neurodegeneration. Key features: Focus on disease-modifying intervention against neurodegenerative diseases, Detailed description of protein quality control pathways, their role in the CNS, and their impairment in neurodegenerative diseases, Judicious selection and full description of validated molecular targets in the pathologically impaired processes of chaperone refolding, the ubiquitin-proteasome system, macro-autophagy, aggrephagy, and protein aggregation, Forty-five full color figures representing functional physiological pathways and their impaired pathological state in disease, along with the biophysical aggregation process of Tau and selected molecular targets from the Hsp family, the ubiquitin-proteasome, and autophagy machineries, A related chemistry-oriented book, Chemical Modulators of Protein Misfolding and Neurodegenerative Disease, is also forthcoming, which will thoroughly describe the small molecule modulators of these targets Book jacket.

Contents:

1 Protein Misfolding, Neurodegeneration and Tau

1.1 The neurodegeneration scenario 1

1.2 Protein folding: physiological benefits and pathological consequences 3

1.3 Tau: An intrinsically disordered, flexible, and aggregation-prone protein 10

1.4 Tauopathies: Aggregation-prone tau in neurodegenerative disease (NDD) 15

2 Targeting the Protein Quality Control (PQC) Machinery

2.1 Molecular chaperones, PQC, and neurodegeneration 39

2.2 Molecular targets 41

2.3 Disease-modifying compounds 49

3 Proteasomal Degradation of Soluble, Misfolded Proteins

3.1 UPS-mediated degradation of misfolded proteins 75

3.2 UPS-mediated degradation of misfolded proteins in NDDs 98

3.3 UPS-targets 100

3.4 Disease-modifying compounds 109

4 Unselective Disposal of Cellular Aggregates

4.1 Autophagy-mediated degradation of protein aggregates 135

4.2 Autophagy-mediated degradation of protein aggregates in NDDs 154

4.3 Macroautophagy-targets 157

4.4 Disease-modifying compounds 162

5 Selective Disposal of Insoluble Protein Aggregates

5.1 Aggrephagy-mediated degradation of protein aggregates 183

5.2 Selective autophagy-mediated degradation of protein aggregates in NDDs 191

5.3 Selective autophagy-targets 192

5.4 Disease-modifying compounds 211

6 Assembly and Disassembly of Protein Aggregates

6.1 Introduction 229

6.2 Disordered protein aggregates and ordered amyloid fibrils 229

6.3 Chaperone-driven disaggregation of protein aggregates 253

6.4 Disease-modifying compounds 258.

Notes:

Electronic reproduction. Palo Alto, Calif. Available via World Wide Web.

Description based on print version record.

Local Notes:

Acquired for the Penn Libraries with assistance from the Gail and Warren Lieberfarb Mental Health and Neuroscience Library Resources Fund.

ISBN:

0128004991

9780128004999

Publisher Number:

99960546490

Access Restriction:

Restricted for use by site license.