World Scientific Publishing Company AUTOPHAGY OF THE NERVOUS SYSTEM: CELLULAR SELF-DIGESTION IN NEURONS AND NEUROLOGICAL DISEASES

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. From the Back Cover What is autophagy? Why would neurons or other brain cells digest parts of themselves through autophagy? How can autophagy save the lives of cells under some conditions, but act as a culprit or accomplice to cell death in others? How does dysfunction of autophagy contribute to neurological diseases and can it be repaired or restored? This book addresses these questions and provide an expert view of the emerging concepts in autophagy research, focusing on autophagic processes and regulation in neurons. Current experimental evidence for both evolutionarily conserved and specialized regulatory mechanisms for autophagy in the mammalian nervous system will be presented. Advances in our understanding of the complex interplay of autophagy induction and downregulation will be discussed in relation to the critical balance needed to modulate neuroprotection versus neurodegeneration in the context of neurological diseases including Alzheimer's, Parkinson's, Huntington's, ischemic-hypoxic and lysosomal diseases.