Enhancement of Mitochondrial Function by the Neurogenic Molecule NSI-189 Accompanies Reversal of Peripheral Neuropathy and Memory Impairment in a Rat Model of Type 2 Diabetes.

Aims: Mitochondrial dysfunction contributes to many forms of peripheral and central nervous system degeneration. Therapies that protect mitochondrial number and function have the potential to impact the progression of conditions such as diabetic neuropathy. We therefore assessed indices of mitochondrial function in dorsal root ganglia (DRG) and brain cortex of the Zucker diabetic fatty (ZDF) rat model of type 2 diabetes and tested the therapeutic impact of a neurogenic compound, NSI-189, on both mitochondrial function and indices of peripheral and central neurological dysfunction.

Ubiquitination and deubiquitination of 4E-T regulate neural progenitor cell maintenance and neurogenesis by controlling P-body formation.

During embryogenesis, neural stem/progenitor cells (NPCs) proliferate and differentiate to form brain tissues. Here, we show that in the developing murine cerebral cortex, the balance between the NPC maintenance and differentiation is coordinated by ubiquitin signals that control the formation of processing bodies (P-bodies), cytoplasmic membraneless organelles critical for cell state regulation. We find that the deubiquitinase Otud4 and the E3 ligase Trim56 counter-regulate the ubiquitination status of a core P-body protein 4E-T to orchestrate the assembly of P-bodies in NPCs.

Immunohistochemical analysis of the developing mouse cortex.

The cerebral cortex is the most complex structure in the mammalian brain, whose development requires coordinated proliferation of neural stem/precursor cells (NPCs) and their differentiation into neurons and glia. Perturbations in NPC homeostasis can lead to abnormal cortical development which is frequently seen in neurodevelopmental disorders. In this chapter, we describe the preparation of cortical tissues from mice and step-by-step protocol for immunohistochemistry to study cortical development.

Development of iPSC-based clinical trial selection platform for patients with ultrarare diseases.

A "Leap-of-Faith" approach is used to treat patients with previously unknown ultrarare pathogenic mutations, often based on evidence from patients having dissimilar but more prevalent mutations. This uncertainty reflects the need to develop personalized prescreening platforms for these patients to assess drug efficacy before considering clinical trial enrollment. In this study, we report an 18-year-old patient with ultrarare Leigh-like syndrome.