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Tauopathies are neurodegenerative disorders with increasing incidence and still without cure. The extensive time required for development and approval of novel therapeutics highlights the need for testing and repurposing known safe molecules. Since doxycycline impacts α-synuclein aggregation and toxicity, herein we tested its effect on tau. We found that doxycycline reduces amyloid aggregation of the different isoforms of tau protein in a dose-dependent manner, remodeling the resultant species. Furthermore, doxycycline interacts with tau microtubule-binding domain preventing its aggregation. In a cell free system doxycycline also prevents tau seeding and in cell culture reduces toxicity of tau aggregates. Overall, our results expand the spectrum of action of doxycycline against aggregation-prone proteins, opening novel perspectives for its repurposing as a disease-modifying drug for tauopathies.

Clinical psychological science is a field committed to reducing the negative impact of psychiatric illness through innovative research and psychological treatments. Unfortunately, the impact of racial injustices that pervade American society and permeate our academic institutions is felt not only by the individuals who work in our departments as faculty, staff, and students, but also by those who seek our services as mental health providers. Representing the collective work of numerous graduate students and postdoctoral trainees from multiple institutions, this call to action instantiates the need for prompt and consistent efforts towards dismantling institutionalized racism and inequity in clinical science. Specifically, we articulate the multiple roles our field plays in perpetuating racial oppression and outline concrete demands and recommendations for structural reform in the following key areas: (1) the mental health needs of Black, Indigenous, and People of Color (BIPOC) students, (2) clinical training and supervision, (3) curriculum and pedagogical approaches, (4) research and methods, and (5) the recruitment, retention, and success of graduate students and faculty.

Item does not contain fulltext Currently, six inborn errors of metabolism with 3-methylglutaconic aciduria as discriminative feature are known. The "Primary 3-methylglutaconic aciduria," 3-methylglutaconyl-CoA hydratase deficiency or AUH defect, is a disorder of leucine catabolism. For all other subtypes, also denoted "Secondary 3-methylglutaconic acidurias" (TAZ defect or Barth syndrome, SERAC1 defect or MEGDEL syndrome, OPA3 defect or Costeff syndrome, DNAJC19 defect or DCMA syndrome, TMEM70 defect, "not otherwise specified (NOS) 3-MGA-uria"), the origin of 3-methylglutaconic aciduria remains enigmatic but is hypothesized to be independent from leucine catabolism. Here we show the results of leucine loading test in 21 patients with different inborn errors of metabolism who present with 3-methylglutaconic aciduria. After leucine loading urinary 3-methylglutaconic acid levels increased only in the patients with an AUH defect. This strongly supports the hypothesis that 3-methylglutaconic aciduria is independent from leucine breakdown in other inborn errors of metabolism with 3-methylglutaconic aciduria and also provides a simple test to discriminate between primary and secondary 3-methylglutaconic aciduria in regular patient care.