Mitophagy is the selective degradation of mitochondria by autophagy. It consists in the recruitment of defective mitochondria or non-needed in a double-membrane structure, called autophagosome, which transports the mitochondria to the lysosome, where it will be degraded. It is an important process in the maintenance of the cellular homeostasis. The accumulation of defective mitochondria due to a block in mitophagy, or a lack of healthy mitochondria due to excessive mitophagy, can cause a detrimental effect on cellular homeostasis. In fact, it is known to be altered in several pathological conditions, such as in cancer, heart diseases and especially in neurodegenerative diseases like Parkinson’s disease, Alzheimer’s disease, or Amyotrophic Lateral Sclerosis.Thus, mitophagy rises as an interesting therapeutic target in the field of medicinal chemistry and drug discovery. The main objective of this thesis was the discovery of new mitophagy modulators, their characterization, and their therapeutic applicability on models of neurodegeneration.Starting from two chemical libraries with more than 3700 compunds, several filters like computational tools and selection of compounds based on chemical diversity were applied to reduce the number of compounds to be evaluated. Finally, 90 compounds were studied in a phenotypic mitophagy assay. Two mitophagy inducers and one inhibitor were obtained…