Defects of Nutrient Signaling and Autophagy in Neurodegeneration
Jon Ondaro, Haizea Hernández-Eguiazu, Maddi Garciandia-Arcelus, Raúl Loera‐Valencia, Laura Rodríguez-Gómez, Andrés Jiménez-Zúñiga, Julen Goikolea, Patricia Rodriguez‐Rodriguez, Javier Ruiz‐Martínez, Fermín Moreno, Adolfo López de Munaín, Ian Holt, Francisco J. Gil‐Bea, Gorka Gereñu
Abstract
Neurons are post-mitotic cells that allocate huge amounts of energy to the synthesis of new organelles and molecules, neurotransmission and to the maintenance of redox homeostasis. In neurons, autophagy is not only crucial to ensure organelle renewal but it is also essential to balance nutritional needs through the mobilization of internal energy stores. A delicate crosstalk between the pathways that sense nutritional status of the cell and the autophagic processes to recycle organelles and macronutrients is fundamental to guarantee the proper functioning of the neuron in times of energy scarcity. This review provides a detailed overview of the pathways and processes involved in the balance of cellular energy mediated by autophagy, which when defective, precipitate the neurodegenerative cascade of Parkinson's disease, frontotemporal dementia, amyotrophic lateral sclerosis or Alzheimer's disease.