Author’s Reply to Segura-Aguilar: Autophagosome maturation not autophagy induction is impaired in neurodegeneration

• Published in: CNS drugs Vol. 32; no. 7; pp. 687 - 688
• Main Authors: Fowler, Alan J., Moussa, Charbel E.-H.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.07.2018; Springer Nature B.V
• Subjects: Animal models; Autophagosomes; Autophagy; Cell culture; Cytosol; Defects; Dopamine; Dopamine receptors; Humans; Intellectual property; Kinases; Letter to the Editor; Medicine; Medicine & Public Health; Metabolism; Movement disorders; Neurodegeneration; Neurodegenerative diseases; Neurology; Neurons; Neurosciences; Oxidation; Parkinson Disease; Parkinson's disease; Phagocytosis; Phagosomes; Pharmacotherapy; Protein-tyrosine kinase; Proteins; Psychiatry; Psychopharmacology; Synuclein; Toxicity; Transmission electron microscopy; Vacuoles
• ISSN: 1172-7047; 1179-1934
• DOI: 10.1007/s40263-018-0534-4

The manuscript does not claim that the induction of autophagy is impaired, but on the contrary, the transmission electron microscopy images clearly indicate that the problem is not in the induction of autophagy but the clearance of autophagic vacuoles. [...]nilotinib and any other compound that is capable of facilitating clearance of autophagosomes and other pre-lysosomal structures that accumulate in the cytosol can potentially clear toxic proteins that accumulate in these autophagic vacuoles. Genomewide association studies have documented that defects in genes that are implicated in autophagy are not limited to dopaminergic neurons in Parkinson's diseases [12] and extensive evidence in cell culture, animal models and humans indicate alpha-synuclein accumulation and toxicity as well as defects in autophagy in almost every type of cell that has been studied. Moussa is listed as an inventor on a Georgetown University intellectual property patent to use tyrosine kinase inhibitors for the treatment of neurodegenerative diseases.