Autophagy is essential for oligodendrocyte differentiation, survival, and proper myelination.

Deficient myelination, the spiral wrapping of highly specialized membrane around axons, causes severe neurological disorders. Maturation of oligodendrocyte progenitor cells (OPC) to myelinating oligodendrocytes (OL), the sole providers of central nervous system (CNS) myelin, is tightly regulated and involves extensive morphological changes. Here, we present evidence that autophagy, the targeted isolation of cytoplasm and organelles by the double-membrane autophagosome for lysosomal degradation, is essential for OPC/OL differentiation, survival, and proper myelin development.

Blocking Autophagy in Oligodendrocytes Limits Functional Recovery after Spinal Cord Injury.

Autophagy mechanisms are well documented in neurons after spinal cord injury (SCI), but the direct functional role of autophagy in oligodendrocyte (OL) survival in SCI pathogenesis remains unknown. Autophagy is an evolutionary conserved lysosomal-mediated catabolic pathway that ensures degradation of dysfunctional cellular components to maintain homeostasis in response to various forms of stress, including nutrient deprivation, hypoxia, reactive oxygen species, DNA damage, and endoplasmic reticulum (ER) stress. Using pharmacological gain and loss of function and genetic approaches, we investigated the contribution of autophagy in OL survival and its role in the pathogenesis of thoracic contusive SCI in female mice.

Active Cdk5 Immunoprecipitation and Kinase Assay.

Cdk5 activity is regulated by the amounts of two activator proteins, p35 and p39 (Tsai , 1994; Zheng , 1998; Humbert , 2000). The p35-Cdk5 and p39-Cdk5 complexes have differing sensitivity to salt and detergent concentrations (Hisanaga and Saito, 2003; Sato , 2007; Yamada , 2007; Asada , 2008). Cdk5 activation can be directly measured by immunoprecipitation of Cdk5 with its bound activator, followed by a Cdk5 kinase assay.

p39 Is Responsible for Increasing Cdk5 Activity during Postnatal Neuron Differentiation and Governs Neuronal Network Formation and Epileptic Responses.

Unlabelled: Two distinct protein cofactors, p35 and p39, independently activate Cyclin-dependent kinase 5 (Cdk5), which plays diverse roles in normal brain function and the pathogenesis of many neurological diseases. The initial discovery that loss of p35 impairs neuronal migration in the embryonic brain prompted intensive research exploring the function of p35-dependent Cdk5 activity. In contrast, p39 expression is restricted to the postnatal brain and its function remains poorly understood.

Does the preclinical evidence for functional remyelination following myelinating cell engraftment into the injured spinal cord support progression to clinical trials?

This article reviews all historical literature in which rodent-derived myelinating cells have been engrafted into the contused adult rodent spinal cord. From 2500 initial PubMed citations identified, human cells grafts, bone mesenchymal stem cells, olfactory ensheathing cells, non-myelinating cell grafts, and rodent grafts into hemisection or transection models were excluded, resulting in the 67 studies encompassed in this review. Forty five of those involved central nervous system (CNS)-derived cells, including neural stem progenitor cells (NSPCs), neural restricted precursor cells (NRPs) or oligodendrocyte precursor cells (OPCs), and 22 studies involved Schwann cells (SC).

Remyelinating Oligodendrocyte Precursor Cell miRNAs from the Sfmbt2 Cluster Promote Cell Cycle Arrest and Differentiation.

Unlabelled: Oligodendrocyte (OL) loss contributes to the functional deficits underlying diseases with a demyelinating component. Remyelination by oligodendrocyte progenitor cells (OPCs) can restore these deficits. To understand the role that microRNAs (miRNAs) play in remyelination, 2',3'-cyclic-nucleotide 3'-phosphodiesterase-EGFP(+) mice were treated with cuprizone, and OPCs were sorted from the corpus callosum.

p39, the primary activator for cyclin-dependent kinase 5 (Cdk5) in oligodendroglia, is essential for oligodendroglia differentiation and myelin repair.

Cyclin-dependent kinase 5 (Cdk5) plays key roles in normal brain development and function. Dysregulation of Cdk5 may cause neurodegeneration and cognitive impairment. Besides the well demonstrated role of Cdk5 in neurons, emerging evidence suggests the functional requirement of Cdk5 in oligodendroglia (OL) and CNS myelin development.

Oligodendroglia and neurotrophic factors in neurodegeneration.

Myelination by oligodendroglial cells (OLs) enables the propagation of action potentials along neuronal axons, which is essential for rapid information flow in the central nervous system. Besides saltatory conduction, the myelin sheath also protects axons against inflammatory and oxidative insults. Loss of myelin results in axonal damage and ultimately neuronal loss in demyelinating disorders.

The star family member QKI and cell signaling.

The family of Signal Transduction and Activators of RNA (STAR) is named based on the intriguing potential for these proteins to connect cell signaling directly to the homeostasis of their mRNA ligands. Besides the commonly shared single RNA binding domain that displays heterogeneous nuclear ribonucleoprotein K homology (KH), STAR proteins also harbor domains predicted to bind critical components in signal transduction pathways, in particular the Src-family protein tyrosine kinases (Src-PTKs). Indeed, accumulating evidence in recent years has demonstrated that the RNA-binding activity and the homeostasis of downstream mRNA targets of STAR proteins can be regulated by phosphorylation in response to various extracellular signals.