Autophagy in Health and Disease

Autophagy in Health and Disease, Second Edition provides a comprehensive overview of the process of autophagy and its impact on human physiology and pathophysiology. The editors expand the coverage from the 1st edition – focused on the cardiovascular system, where research started - to all cell types and organ systems.

Starting with the foundational concepts, part I provides an overview of the area, including: history, trajectory of the research field, mechanisms of autophagy, and its regulation. Part I also cover developmental aspects, including: stem cells, embryogenesis, hematopoiesis, and paligenosis. Part II is devoted to applications to several systems in the human body including: Metabolic control and Diabetes, Cardiovascular, Nervous, Immune, Gastrointestinal, and Skeletal. The final chapters provide additional disease considerations, covering cancer, longevity, disease mechanisms, and the therapeutic targeting of Autophagy.

This book is invaluable to anyone new to the field, as well as established investigators who are looking for a broader understanding of autophagy outside their specific field of study.

• Provides a comprehensive overview of the process of autophagy and its impact on human physiology and pathophysiology
• Extended coverage of the mechanisms mediating autophagy
• Coverage the role of autophagy in stem cells and iPSCs, as well as the regenerative process of “paligenosis”
• New sections on Metabolic Control and Diabetes include separate chapters covering the liver, adipose, pancreas, and skeletal muscle
• New section will on the nervous system and neurodegeneration
• New chapter on cancer and cancer therapeutics

Researchers, graduate students, and professionals studying autophagy across cell biology, biochemistry, medicine, and biomedical sciences

A. Overview
1. Introduction –
- history and trajectory (Nobel prize, apoptosis)
- Types of Autophagy: Macro, micro, chaperone-mediated and chaperone assisted autophagy
2. Mechanisms of autophagy – the machinery of macroautophagy & points of control
3. Regulation of autophagy- transcriptional, post-transcriptional, translational and post-translational
4. Selectivity and trafficking of autophagic cargos
- mitophagy, lipophagy, ER-phagy, ribophagy, nucleophagy, lysosomophagy, inflammasomophagy, etc. along with cargo linkers
- Contribution to endocytosis, macropincocytosis, phagocytosis and exocytosis
5. Role of Lysosomes in autophagy:
- Impact of lysosome function on autophagy (lysosome storage diseases and acquired lysosome dysfunction)
- LYNUS (lysosome nutrient sensing complex) regulation of autophagy via the TFE/MiT family of transcription factors.
6. Methods for studying autophagy
7. Effects of Physiologic Inputs on Autophagy (with considerations of the impact of gender, fasting/feeding, circadian rhythms, exercise and aging)

B. Development
8. Stem cells and iPSCs
-Role of autophagy in stem cell development and sustenance
9. Embryogenesis
-Role of autophagy in organismal development
10. Hematopoiesis
-Role of autophagy in mammalian hematopoiesis, as a special case of stem cell homeostasis.
11. Paligenosis

C. Metabolic control and diabetes
12. Liver
- Role of autophagy in liver homeostasis and pathology, with particular emphasis on diabetes and fatty liver diseases
13. Adipose
- Role of autophagy in adipose tissue development and obesity
14. Pancreas
- Role of autophagy in diseases of endocrine and exocrine pancreas, with a focus on diabetes and pancreatitis
15. Skeletal muscle
- Autophagy in skeletal muscle health, exercise physiology and regeneration; and in diseases of the skeletal muscle.

D. Cardiovascular system
16. Heart
- Autophagy in cardiac development and regeneration
- Autophagy in cardiac myocytes in homeostasis and stress response, with emphasis on myocardial infarction, cardiomyopathies and arrhythmic disorders
- Autophagy in cardiac immune cells
- Autophagy in cardiac fibroblasts as a regulator of fibrosis
17. Lungs
- Autophagy in lung development
- Autophagy in diseases of the respiratory system.
18. Vasculature
- Autophagy in atherosclerosis
- Autophagy regulation of endothelial function and blood pressure

E. The nervous system and neurodegeneration
19. Autophagy in neurons and the CNS: function and homeostasis
- Autophagy in neurons, astrocytes, and other glial cell types
- Role in normal function of the synapse;
- Normal cycling of presynaptic vesicles and the intersection with autophagy;
- Proteostasis at the postsynapse;
- challenges and processes of trafficking autophagosomes from axons to soma;
- Autophagy in the interplay between astrocytes and neurons;
- Glycogen clearance (Lafora Disease), lysosomal storage disease
20. Altered mitophagy on the path to Parkinsons disease
21. Autophagic processes in early- and late- onset Alzheimer’s disease.
22. Autophagic involvement in other neurodegenerative disorders
- ALS, FTLD, SMA
(mutations in SQSTM1 are linked to ALS)

F. Homeostasis and disease in other organ systems
23. Autophagy as an integral component of the immune system (including infection and sepsis)
- Dealing with Invading pathogens, and subversive actions of invaders
- Antigen presentation
- Innate immunity
- Adaptive immunity
- Mitochondrial antigen presentation and autoimmunity
24. Autophagy in the gastrointestinal system and cross-talk with microbiota
- Crohn disease
- Chronic colitis
- Secretory autophagy – (can we get Laura Hooper?)
- The intestinal barrier
25. Autophagy in building and maintaining the skeletal system
- Autophagy in osteoblast and osteocyte function
- Autophagy in osteoclast formation and function
- Diseases of bone and cartilage

G. Additional disease considerations
26. Autophagy on the road to longevity and aging
27. Autophagy in cancer, friend or foe?
28. Micro autophagy mechanisms and disease
29. Chaperone mediated autophagy mechanisms and disease
30. Therapeutic targeting of Autophagy, lifestyle and pharmacology.