Autophagy of the Nervous System. Cellular Self-Digestion in Neurons and Neurological Diseases

Description

What is autophagy? Why would neurons digest parts of themselves through autophagy? How can autophagy save the lives of cells under some conditions, but act as an accomplice to cell death in others? By what mechanisms are autophagy-related processes dysregulated in neurological diseases, and are there therapeutic strategies to correct or compensate for their dysfunction? This book provides an expert view of major concepts in autophagy research with a focus on autophagy in neurons. Experimental evidence for evolutionarily conserved and specialized regulatory mechanisms for autophagy in the mammalian nervous system will be presented, including recent data on braking mechanisms. Areas of intersection with cell death, the ubiquitin-proteasome system, chaperone-mediated autophagy, and the endocytic pathway will be reviewed, along with emerging areas of mitochondrial autophagy (mitophagy) and the autophagic regulation of neuritic/synaptic processes. Advances in delineating mechanisms by which autophagy is involved in the pathophysiology of neurological disorders, including Alzheimer's, Parkinson's, Huntington's, amyotrophic lateral sclerosis, ischemia/hypoxia and lysosomal storage diseases, will be discussed along with current drug development strategies targeting autophagy.

Contents:

Neuronal Autophagy: Cellular Process and Regulation:

• The Cellular Process of Autophagy and Control of Autophagy in Neurons (Nicole C McKnight, Noboru Mizushima and Zhenyu Yue)
• Autophagosome Maturation, Endocytosis and Neurodegenerative Disease (Ai Yamamoto and Anne Simonsen)
• Cross-Talk Between the Ubiquitin-Proteasome System and Macroautophagy (Serhiy Pankiv and Terje Johansen)
• Chaperone-Mediated Autophagy (CMA) in Neurons (Maria Xilouri, Hsiao-Yu Peng and Leonidas Stefanis)
• Maintaining Autophagic Balance: A Role for Brakes (Salvatore J Cherra, III and Charleen T Chu)

Autophagy and Neurological Diseases:

• Autophagy and Its Cross-Talk with Cell Death in Neural Development (Sabrina Di Bartolomeo and Francesco Cecconi)
• Autophagy in the Retina: Development, Physiology and Pathology (Patricia Boya)
• Genetic Mouse Models for Elucidation of Autophagy-Lysosomal Systems in Neurons Under Physiologic and Pathologic Conditions (Masaaki Komatsu, Masato Koike, Yoshinobu Ichimura and Yasuo Uchiyama)
• Autophagy in Amyotrophic Lateral Sclerosis (Jozsef Gal and Haining Zhu)
• Autophagy Failure in Alzheimer's Disease and Lysosomal Storage Disorders: A Common Pathway to Neurodegeneration? (Devin M Wolfe and Ralph Nixon)
• Autophagy in Huntington's and Parkinson's Diseases: Pathogenic Mechanism and Therapeutic Potentials (Junghyun Lim, Lauren G Friedman, Nicole C McKnight and Zhenyu Yue)
• Metabolism, Autophagy and Neurodegeneration (W Haung Yu and Karen E Duff)
• The Potential of Autophagy Regulation in the Treatment of Neurodegenerative Diseases (Ashley R Winslow, Zeyn W Green-Thompson and David C Rubinsztein)
• Lysosome Storage Disorders on the Brain: The Autophagy-Lysosome Pathway Contributes to Disease Pathophysiology and May be Utilized for Therapeutic Benefit (John J Shacka)

Specialized Autophagy: The New Frontier:

• Autophagy — Roles in Synaptic Structure and Function (Daniela Hernandez and David Sulzer)
• Neuronal Mitochondrial Transport and Turnover via Mitophagy (Zu-Hang Sheng and Charleen T Chu)
• Role of Autophagy in Neurite Degeneration In Vitro (Yi Yang, Xiaoxiang Zheng and Tatsuro Koike)