The final section considers biophysical methods, molecular dynamics, and machine learning approaches in the study of these aspects. The book provides a detailed overview of protein dysfunction and its implications for health and disease, aiding understanding of protein condensates and aggregates, protein misfolding, co-chaperoning and toxicity of pre-amyloid aggregates. By understanding the fundamental properties underlying these, the book paves the way for investigating how proteinopathies could be treated.
Table of Contents
Part 1. Protein aggregation in different proteinopathies1. Amyloid-pore hypothesis: prefibrillar oligomers interaction with membranes; a generic cause of neurodegeneration?
2. In vivo molecular brain imaging of metabolic (dys)function and protein accumulation in neurodegenerative disease
3. Amyotrophic lateral sclerosis: Relevance of protein aggregation of TDP-43 and mechanisms of toxicity
4. Cystatin C amyloid angiopathy (CAA) and AD: Interaction of cystatins oligomers with A-beta
5. Protein aggregation and disturbed proteostasis in mental illness, stress on shizophrenia
6. Protein aggregation in progressive myoclonus epilepsies, in particular EPM1
7. Model amyloid proteins: What are the lessons to understand proteinopathies
Part 2. Common signaling pathways and biomarkers of disease
8. The integrated stress response: from mechanism to disease
9. Comparison of AD and schizophrenia: From signaling to biomarkers
10. Oxidative stress and mitochondrial decline in common to several proteinopathies
11. Irisin reduces amyloid-b by inducing the release of neprilysin from astrocytes following down regulation of ERK-STAT3 signaling
12. Dysregulated molecular pathways in amyotrophic lateral sclerosis-frontotemporal dementia spectrum disorder
Part 3. Small molecules as modulators of the key processes in proteinopathies
13. Trem2 signaling modulators to treat neurodegenerative disease
14. Small molecules modulators of protein aggregation and toxicity: antioxidants and polyphenol compounds
15. Therapeutic Strategies to Mitigate the Toxicity of ?-Synuclein Oligomers in Parkinson's Disease
16. Repurposed drugs that modulate proteinopathies
17. Future of metal chelators in AD therapy
18. Novel dual-acting hybrids targeting type-2 cannabinoid receptors and cholinesterase activity show neuroprotective effects in vitro and amelioration of cognitive impairment in vivo
19. Role of autophagy in neurodegeneration and aging; small molecule modulators
20. NEW treatments on the horizon for Alzheimer’s and other neurodegenerative diseases
Part 4. Modern biophysical methods, molecular dynamics and machine learning
21. Intrinsically unfolded proteins and the role of protein condensation
22. A-beta: Structure and interaction with membranes as revealed by NMR
23. Oligomers formation by amyloid beta as studied by coarse-grain MD
24. Machine learning in prediction of protein aggregation and/or condensation states
Authors
Eva Zerovnik Department of Biochemistry and Molecular and Structural Biology, Jozef Stefan Institute, 1000, Ljubljana, Slovenia; and Jozef Stefan International Postgraduate School (IPS), 1000 Ljubljana, Slovenia.Eva Zerovnik is known in the field of protein folding and in neuroscience. She publishes in both fields, as well as biophysics. Her educational background is in physical chemistry, structural biology, biochemistry and neurosciences, therefore her work is multidisciplinary. She is currently Professor of Biochemistry at Jozef Stefan International Postgraduate School and scientific advisor at Institut Jozef Stefan, Slovenia. She has led collaborations with some leading labs such as Medical School, Nottingham, Medical School, Newcastle upon Tyne, Biomolecular NMR, Sheffield, UK, Department of Physics, Drexel University USA, Brain and Mind Institute, Lausanne, CH and IRCCS Fatebenefratelli, Brescia, Italy.
Robert Layfield Professor of Protein Biochemistry, The University of Nottingham Medical School Queen's Medical Centre Nottingham, UK.Robert Layfield is a Professor of Protein Biochemistry at the University of Nottingham. He recently completed a 4-year term as Head of the Physiology, Pharmacology and Neuroscience Research Division, within the School of Life Sciences. He was an MND Association BRAP (Biomedical Research Advisory Panel) member from 2018-2022 and has a long-standing research interest in cellular mechanisms of removal of defective proteins in Alzheimer's disease, Parkinson's and MND. His group made the first mechanistic demonstrations of proteostasis defects in Alzheimer's disease.
