Combined clinical, structural, and cellular studies discriminate pathogenic and benign TRPV4 variants.

Dominant mutations in the calcium-permeable ion channel TRPV4 (transient receptor potential vanilloid 4) cause diverse and largely distinct channelopathies, including inherited forms of neuromuscular disease, skeletal dysplasias, and arthropathy. Pathogenic TRPV4 mutations cause gain of ion channel function and toxicity that can be rescued by small molecule TRPV4 antagonists in cellular and animal models, suggesting that TRPV4 antagonism could be therapeutic for patients. Numerous variants in TRPV4 have been detected with targeted and whole exome/genome sequencing, but for the vast majority, their pathogenicity remains unclear.

Disruption of axonal transport in neurodegeneration.

Neurons are markedly compartmentalized, which makes them reliant on axonal transport to maintain their health. Axonal transport is important for anterograde delivery of newly synthesized macromolecules and organelles from the cell body to the synapse and for the retrograde delivery of signaling endosomes and autophagosomes for degradation. Dysregulation of axonal transport occurs early in neurodegenerative diseases and plays a key role in axonal degeneration.

Engagement of Neurotropic Viruses in Fast Axonal Transport: Mechanisms, Potential Role of Host Kinases and Implications for Neuronal Dysfunction.

Much remains unknown about mechanisms sustaining the various stages in the life cycle of neurotropic viruses. An understanding of those mechanisms operating before their replication and propagation could advance the development of effective anti-viral strategies. Here, we review our current knowledge of strategies used by neurotropic viruses to undergo bidirectional movement along axons.

Secondary Causes of Myositis.

Purpose Of Review: The purpose of this paper is to comprehensively evaluate secondary causes of inflammatory myopathies (myositis) and to review treatment options.

Recent Findings: This review highlights recent advancements in our understanding of known causes of myositis, including newer drugs that may cause myositis such as checkpoint inhibitors and viruses such as influenza, HIV, and SARS-CoV2. We also discuss treatment for malignancy-associated myositis and overlap myositis, thought to be a separate entity from other rheumatologic diseases.

Adolescent-onset absence epilepsy years after resolution of childhood epilepsy with myoclonic-atonic seizures.

We present a case series of three boys with childhood epilepsy with myoclonic-atonic seizures (EMAS) who achieved complete remission during childhood only to develop absence seizures during early adolescence. In all three cases, the recurrent seizures resolved again with antiseizure drugs, and two are currently medication-free for a second time.

HIV Glycoprotein Gp120 Impairs Fast Axonal Transport by Activating Tak1 Signaling Pathways.

Sensory neuropathies are the most common neurological complication of HIV. Of these, distal sensory polyneuropathy (DSP) is directly caused by HIV infection and characterized by length-dependent axonal degeneration of dorsal root ganglion (DRG) neurons. Mechanisms for axonal degeneration in DSP remain unclear, but recent experiments revealed that the HIV glycoprotein gp120 is internalized and localized within axons of DRG neurons.

Virus-induced neuronal dysfunction and degeneration.

In general, virus infections of the brain are rather rare in the immune competent host. However, neurotropic viruses have developed mechanisms to exploit weaknesses in immunological defense mechanisms that eventually allow them to reach and infect CNS neurons. Once in the CNS, these viruses can induce significant neuronal dysfunction and degeneration of specific neuronal populations, sometimes leading to devastating, life-threatening consequences for the host.