New evidence of vascular defects in neurodegenerative diseases revealed by single cell RNA sequencing.

Neurodegenerative diseases (NDs) involve the progressive loss of neuronal structure or function in the brain and spinal cord. Despite their diverse etiologies, NDs manifest similar pathologies. Emerging research identifies vascular defects as a previously neglected hallmark of NDs.

HnRNPR strongly represses splicing of a critical exon associated with spinal muscular atrophy through binding to an exonic AU-rich element.

Background: Spinal muscular atrophy (SMA) is a motor neuron disease caused by mutations of survival of motor neuron 1 ) gene, which encodes the SMN protein. , a nearly identical copy of , with several single-nucleotide substitutions leading to predominant skipping of its exon 7, is insufficient to compensate for loss of . Heterogeneous nuclear ribonucleoprotein R (hnRNPR) has been previously shown to interact with SMN in the 7SK complex in motoneuron axons and is implicated in the pathogenesis of SMA.

Position-dependent effects of hnRNP A1/A2 in SMN1/2 exon7 splicing.

Heterogeneous nuclear ribonucleoprotein A1 and A2 (hnRNP A1/2) is a ubiquitously expressed RNA binding protein known to bind intronic or exonic splicing silencer. Binding of hnRNP A1/2 to survival of motor neuron gene (SMN1/2) exon 7 and flanking sequences strongly inhibits the inclusion of exon 7, which causes spinal muscular atrophy, a common genetic disorder. However, the role of hnRNP A1/2 on the side away from exon 7 is unclear.

Single-cell RNA sequencing reveals dysregulation of spinal cord cell types in a severe spinal muscular atrophy mouse model.

Although spinal muscular atrophy (SMA) is a motor neuron disease caused by the loss of survival of motor neuron (SMN) proteins, there is growing evidence that non-neuronal cells play important roles in SMA pathogenesis. However, transcriptome alterations occurring at the single-cell level in SMA spinal cord remain unknown, preventing us from fully comprehending the role of specific cells. Here, we performed single-cell RNA sequencing of the spinal cord of a severe SMA mouse model, and identified ten cell types as well as their differentially expressed genes.

History of development of the life-saving drug "Nusinersen" in spinal muscular atrophy.

Spinal muscular atrophy (SMA) is an autosomal recessive disorder with an incidence of 1/6,000-1/10,000 and is the leading fatal disease among infants. Previously, there was no effective treatment for SMA. The first effective drug, nusinersen, was approved by the US FDA in December 2016, providing hope to SMA patients worldwide.

Polymeric nanomedicines targeting hematological malignancies.

Hematological malignancies (HMs) typically persisting in the blood, lymphoma, and/or bone marrow invalidate surgery and local treatments clinically used for solid tumors. The presence and drug resistance nature of cancer stem cells (CSCs) further lends HMs hard to cure. The development of new treatments like molecular targeted drugs and antibodies has improved the clinical outcomes for HMs but only to a certain extent, due to issues of low bioavailability, moderate response, occurrence of drug resistance, and/or dose-limiting toxicities.

SMN deficiency causes pain hypersensitivity in a mild SMA mouse model through enhancing excitability of nociceptive dorsal root ganglion neurons.

Spinal muscular atrophy (SMA) is a devastating motor neuron degeneration disease caused by a deficiency of the SMN protein. Majority of patients also suffer from chronic pain. However, the pathogenesis of pain in the context of SMA has never been explored.

Adrenergic stimulation sensitizes TRPV1 through upregulation of cystathionine β-synthetase in a rat model of visceral hypersensitivity.

The pathogenesis of pain in irritable bowel syndrome (IBS) is poorly understood and treatment remains difficult. The present study was designed to investigate roles of adrenergic signaling and the endogenous hydrogen sulfide producing enzyme cystathionine β-synthetase (CBS) in a previously validated rat model of IBS induced by neonatal colonic inflammation (NCI). Here we showed that NCI-induced visceral hypersensitivity (VH) was significantly attenuated by β2 subunit inhibitor but not by β1 or β3 or α subunit inhibitor.

Neonatal colonic inflammation sensitizes voltage-gated Na(+) channels via upregulation of cystathionine β-synthetase expression in rat primary sensory neurons.

The pathogenesis of pain in irritable bowel syndrome (IBS) is poorly understood, and treatment remains difficult. We have previously reported that colon-specific dorsal root ganglion (DRG) neurons were hyperactive in a rat model of IBS induced by neonatal colonic inflammation (NCI). This study was designed to examine plasticity of voltage-gated Na(+) channel activities and roles for the endogenous hydrogen sulfide-producing enzyme cystathionine β-synthetase (CBS) in chronic visceral hyperalgesia.

Upregulation of cystathionine β-synthetase expression contributes to visceral hyperalgesia induced by heterotypic intermittent stress in rats.

Background: Hydrogen sulfide (H₂S) functions as a neuromodulator, but whether it modulates visceral pain is not well known. This study was designed to determine the role for the endogenous H₂S producing enzyme cystathionine β-synthetase (CBS) and cystathionine γ-lyase (CSE) in a validated rat model of visceral hyperalgesia (VH).

Methods: VH was induced by nine-day heterotypic intermittent stress (HIS).