dutasteride and Amyloidosis

In a drug reprofiling attempt, we explored novel neuroprotective properties of 4-azasteroids by synthesizing chemical affinity tags capturing adenine nucleotide translocator-1, as a potential target. Dutasteride inhibits the mitochondrial transition pore and induces an increase of autophagosomal structures in human cell lines. In vivo, a surprising reduction of the beta-amyloid plaque load in a model for cerebral amyloidosis appears to connect release of neurotoxic peptides, mitochondrial apoptosis and autophagy.

Topics: Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Amyloidosis; Animals; Apoptosis; Autophagy; Azasteroids; Brain Diseases; Disease Models, Animal; Dutasteride; Enzyme Inhibitors; Finasteride; Humans; Mice; Mice, Inbred C57BL; Mice, Transgenic; Mitochondrial ADP, ATP Translocases; Mitochondrial Membrane Transport Proteins; Mitochondrial Permeability Transition Pore; N-Methylaspartate; Neocortex; Neurons; Neuroprotective Agents; Plaque, Amyloid; Potassium Cyanide; Presenilins; Sex Factors; Testosterone