Therapeutic indications for HDAC6 inhibitors in the peripheral and central nervous disorders.

Introduction: Inhibition of the enzymatic function of HDAC6 is currently being explored in clinical trials ranging from peripheral neuropathies to cancers. Advances in selective HDAC6 inhibitor discovery allowed studying highly efficacious brain penetrant and peripheral restrictive compounds for treating PNS and CNS indications.

Areas Covered: This review explores the multifactorial role of HDAC6 in cells, the common pathological hallmarks of PNS and CNS disorders, and how HDAC6 modulates these mechanisms.

Analyzing the L4-5 Segmental Alignment Change of Two Minimally Invasive Prone-Based Interbody Fusions.

Study Design: Retrospective Cohort Study.

Objective: Restoration of lumbar lordosis (LL) is a principal objective during spinal fusion procedures, traditionally focusing on achieving an LL within 10° of the pelvic incidence (PI). Recent studies have demonstrated a relatively constant L4-S1 alignment of 35-40° at L4-S1 and at least 15° at L4-5, regardless of PI.

Advances and challenges in modeling inherited peripheral neuropathies using iPSCs.

Inherited peripheral neuropathies (IPNs) are a group of diseases associated with mutations in various genes with fundamental roles in the development and function of peripheral nerves. Over the past 10 years, significant advances in identifying molecular disease mechanisms underlying axonal and myelin degeneration, acquired from cellular biology studies and transgenic fly and rodent models, have facilitated the development of promising treatment strategies. However, no clinical treatment has emerged to date.

Single-Position Prone Lateral Lumbar Interbody Fusion Technique Guide: Surgical Tips and Tricks.

Lateral lumbar interbody fusion (LLIF) is a popular technique as it allows for the placement of a large interbody implant through a retroperitoneal, transpsoas working corridor. Historically, the interbody is placed with the patient in lateral decubitus and then repositioned to prone for the posterior instrumentation. While this has been an effective and successful technique, removing the interoperative flip would improve the efficiency of these cases.

HDAC3 Inhibition Stimulates Myelination in a CMT1A Mouse Model.

Charcot-Marie-Tooth disease (CMT) is the most common inherited peripheral neuropathy, with currently no effective treatment or cure. CMT1A is caused by a duplication of the PMP22 gene, which leads to Schwann cell differentiation defects and dysmyelination of the peripheral nerves. The epigenetic regulator histone deacetylase 3 (HDAC3) has been shown to negatively regulate myelination as well as its associated signaling pathways, PI3K-AKT and MAPK-ERK.

Expansion sequencing: Spatially precise in situ transcriptomics in intact biological systems.

Methods for highly multiplexed RNA imaging are limited in spatial resolution and thus in their ability to localize transcripts to nanoscale and subcellular compartments. We adapt expansion microscopy, which physically expands biological specimens, for long-read untargeted and targeted in situ RNA sequencing. We applied untargeted expansion sequencing (ExSeq) to the mouse brain, which yielded the readout of thousands of genes, including splice variants.

HDAC6 as a potential therapeutic target for peripheral nerve disorders.

Peripheral neuropathies are a heterogeneous group of diseases that are characterized by a progressive, ascending loss of nerve function arising from the peripheral regions of the limbs. The phenotypic overlap between different types of hereditary and acquired peripheral neuropathies indicates that similar pathophysiological processes are at play. Many downstream pathways in peripheral neurons, such as axonal transport, protein degradation, and interactions with Schwann cells, organelle damage, channelopathies, and neuroinflammatory signaling, have been proposed and each affects peripheral nerves in a negative way.

In Vivo Electrophysiological Measurement of Compound Muscle Action Potential from the Forelimbs in Mouse Models of Motor Neuron Degeneration.

Assessing the functionality of the nerve axon provides detailed information on the progression of neuromuscular disorders. Electrophysiological recordings provide a sensitive approach to measure nerve conduction in humans and rodent models. To broaden the technical possibilities for electromyography in mice, the measurement of compound muscle action potentials (CMAPs) from the brachial plexus nerve in the forelimb using needle electrodes is described here.

HDAC6 is a therapeutic target in mutant GARS-induced Charcot-Marie-Tooth disease.

Peripheral nerve axons require a well-organized axonal microtubule network for efficient transport to ensure the constant crosstalk between soma and synapse. Mutations in more than 80 different genes cause Charcot-Marie-Tooth disease, which is the most common inherited disorder affecting peripheral nerves. This genetic heterogeneity has hampered the development of therapeutics for Charcot-Marie-Tooth disease.

Current Advances and Limitations in Modeling ALS/FTD in a Dish Using Induced Pluripotent Stem Cells.

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two age-dependent multifactorial neurodegenerative disorders, which are typically characterized by the selective death of motor neurons and cerebral cortex neurons, respectively. These two diseases share many clinical, genetic and pathological aspects. During the past decade, cell reprogramming technologies enabled researchers to generate human induced pluripotent stem cells (iPSCs) from somatic cells.

Defective axonal transport: A common pathological mechanism in inherited and acquired peripheral neuropathies.

Peripheral neuropathies are characterized by a progressive and length-dependent loss of peripheral nerve function. This can be caused either by genetic defects, classified as 'inherited peripheral neuropathies', or they can be acquired throughout life. In that case, the disease is caused by various insults such as toxins and mechanical injuries, or it can arise secondary to medical conditions such as metabolic disorders, nutritional deficiencies, inflammation and infections.

Activity of male pheromone of Melanesian rhinoceros beetle Scapanes australis.

Laboratory and field investigations were carried out to investigate the nature and role of the male pheromone emitted by the Dynast beetle Scapanes australis and to develop a mass trapping technique against this major coconut pest in Papua New Guinea. We report the biological data obtained from natural and synthetic pheromone, previously described as an 84:12:4 (w/w) mixture of 2-butanol (1), 3-hydoxy-2-butanone (2), and 2,3-butanediol (3). EAG recordings from natural and synthetic pheromone and a pitfall olfactometer were poorly informative.