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Clinical evidence suggests that most of the neurodegenerative diseases are closely related to autophagy failure. This chapter decodes the evolving molecular interplay of autophagy, highlighting newly uncovered mechanisms and their disruption in neurodegeneration. It includes understanding canonical and non-canonical autophagy pathways, including roles of ATG9 vesicles and the regulatory effect of liquid–liquid phase separation on autophagosome assembly. This chapter also explores autophagy dysregulation in neurodegenerative disorders, from failures at endoplasmic reticulum–mitochondria contact to lysosomal system collapse and unexpected outcomes like disrupted lipid homeostasis and retrotransposon activation. With a rising provocative question, can targeted, organelle-specific autophagy enhancement restore function in the face of global pathway failure?

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Mechanisms of Autophagy and Its Dysregulation in Neurodegenerative Diseases

  • 章节

  • 发表日期：

    2026年

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  • Saroj Singhmura,
  • Sagarika Deepthy Tallapragada,
  • Atreyee Ganguly,
  • Jashabir Chakraborty,
  • Abhishek Basu,
  • Yadu Nandan Dey

摘要

Clinical evidence suggests that most of the neurodegenerative diseases are closely related to autophagy failure. This chapter decodes the evolving molecular interplay of autophagy, highlighting newly uncovered mechanisms and their disruption in neurodegeneration. It includes understanding canonical and non-canonical autophagy pathways, including roles of ATG9 vesicles and the regulatory effect of liquid–liquid phase separation on autophagosome assembly. This chapter also explores autophagy dysregulation in neurodegenerative disorders, from failures at endoplasmic reticulum–mitochondria contact to lysosomal system collapse and unexpected outcomes like disrupted lipid homeostasis and retrotransposon activation. With a rising provocative question, can targeted, organelle-specific autophagy enhancement restore function in the face of global pathway failure?