Neddylation orchestrates the complex transcriptional and posttranscriptional program that drives Schwann cell myelination.

Myelination is essential for neuronal function and health. In peripheral nerves, >100 causative mutations have been identified that cause Charcot-Marie-Tooth disease, a disorder that can affect myelin sheaths. Among these, a number of mutations are related to essential targets of the posttranslational modification neddylation, although how these lead to myelin defects is unclear.

E2F1 and E2F2-Mediated Repression of CPT2 Establishes a Lipid-Rich Tumor-Promoting Environment.

Lipid metabolism rearrangements in nonalcoholic fatty liver disease (NAFLD) contribute to disease progression. NAFLD has emerged as a major risk for hepatocellular carcinoma (HCC), where metabolic reprogramming is a hallmark. Identification of metabolic drivers might reveal therapeutic targets to improve HCC treatment.

HuR/ELAVL1 drives malignant peripheral nerve sheath tumor growth and metastasis.

Cancer cells can develop a strong addiction to discrete molecular regulators, which control the aberrant gene expression programs that drive and maintain the cancer phenotype. Here, we report the identification of the RNA-binding protein HuR/ELAVL1 as a central oncogenic driver for malignant peripheral nerve sheath tumors (MPNSTs), which are highly aggressive sarcomas that originate from cells of the Schwann cell lineage. HuR was found to be highly elevated and bound to a multitude of cancer-associated transcripts in human MPNST samples.

Analyzing Autophagic Flux in Nerve Cultures.

Autophagy is a key cellular mechanism involved in the degradation of long-lived proteins and organelles. We and others have previously shown that Schwann cells are able to degrade their own myelin by a form of selective autophagy, or myelinophagy. There is now increasing evidence that myelinophagy could also be aberrantly activated in other demyelinating diseases, including hereditary or inflammatory neuropathies, implicating this pathway in the pathogenesis of these disorders.

Isolation and Purification of Primary Rodent Schwann Cells.

Schwann cells are the main glial cells of the peripheral nervous system (PNS) and play key roles in peripheral nerve development and function, including providing myelin that is essential for normal movement and sensation in the adult. Schwann cells can be readily destabilized by a wide variety of distinct conditions that range from nerve injury to immune assaults, metabolic disturbances, microbial infections, or genetic defects, leading to the breakdown of myelin (demyelination) and a subsequent switch in phenotypic states. This striking feature of Schwann cells forms the cornerstone of several debilitating and even fatal PNS neurological disorders that include the demyelinating neuropathies Guillain Barré syndrome (GBS) and Charcot-Marie-Tooth disease (CMT), and PNS cancers, including Neurofibromatosis.