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Full Description
Molecular Insights into Proteinopathies: Increased Scope from Neurodegeneration to other Pathologies of the Brain investigates the molecular events that lead to various diseases. The book is divided into four parts, the first of which delves into protein aggregation across a range of diseases, including Alzheimer's disease, Parkinson's disease, schizophrenia, neuropsychiatric disease. It then moves on to discuss signaling pathways and biomarkers of disease, including oxidative stress, mitochondrial decline, and dysregulated molecular pathways. The third part explores small molecules as modulators of key processes in the pathogenesis of proteinopathies, including antioxidants, polyphenol compounds, metal chelators, and repurposed drugs that modulate proteinopathies. The final section considers biophysical methods, molecular dynamics and machine learning approaches in the study of these aspects. This 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. This book is an ideal reference for researchers working across cell biology, molecular biology, neuroscience and related fields.
Contents
Part 1. Protein aggregation in different proteinopathies
1. 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 α-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
