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Peripheral nerves have the capacity for regeneration, but the rate of regeneration is so slow that many nerve injuries lead to incomplete recovery and permanent disability for patients. Macrophages play a critical role in the peripheral nerve response to injury, contributing to both Wallerian degeneration and nerve regeneration, and their function has recently been shown to be dependent on intracellular metabolism. To date, the impact of their intracellular metabolism on peripheral nerve regeneration has not been studied. We examined conditional transgenic mice with selective ablation in macrophages of solute carrier family 16, member 1 (Slc16a1), which encodes monocarboxylate transporter 1 (MCT1), and found that MCT1 contributed to macrophage metabolism, phenotype, and function, specifically in regard to phagocytosis and peripheral nerve regeneration. Adoptive cell transfer of wild-type macrophages ameliorated the impaired nerve regeneration in macrophage-selective MCT1-null mice. We also developed a mouse model that overexpressed MCT1 in macrophages and found that peripheral nerves in these mice regenerated more rapidly than in control mice. Our study provides further evidence that MCT1 has an important biological role in macrophages and that manipulations of macrophage metabolism can enhance recovery from peripheral nerve injuries, for which there are currently no approved medical therapies., Introduction Recovery from peripheral nerve injury, which can occur as a result of trauma, surgical iatrogenesis, medications, or toxins, depends on a carefully orchestrated series of events within injured axons [...]

Oligodendroglia support axon survival and function through mechanisms independent of myelination, and their dysfunction leads to axon degeneration in several diseases. The cause of this degeneration has not been determined, but lack of energy metabolites such as glucose or lactate has been proposed. Lactate is transported exclusively by monocarboxylate transporters, and changes to these transporters alter lactate production and use. Here we show that the most abundant lactate transporter in the central nervous system, monocarboxylate transporter 1 (MCT1, also known as SLC16A1), is highly enriched within oligodendroglia and that disruption of this transporter produces axon damage and neuron loss in animal and cell culture models. In addition, this same transporter is reduced in patients with, and in mouse models of, amyotrophic lateral sclerosis, suggesting a role for oligodendroglial MCT1 in pathogenesis. The role of oligodendroglia in axon function and neuron survival has been elusive; this study defines a new fundamental mechanism by which oligodendroglia support neurons and axons., Oligodendroglia promote rapid conduction of action potentials by ensheathing central nervous system (CNS) axons with myelin. Oligodendrocyte diseases, such as multiple sclerosis and leukodystrophies, have demonstrated demyelination and axon degeneration [...]

The Peripheral Neuropathy Research Registry (PNRR) is a prospective cohort of peripheral neuropathy (PN) patients focused on idiopathic axonal peripheral neuropathy. Patients with diabetic, human immunodeficiency virus‐, and chemotherapy‐induced peripheral neuropathies are enrolled as comparison groups. The PNRR is a multi‐center collaboration initiated and funded by the Foundation for Peripheral Neuropathy (FPN) with the objective to recruit a well characterized cohort of patients with different phenotypes and symptoms in each diagnostic category, and to advance research through development of biomarkers and identification of previously unknown causes of PN. The overall goal of the initiative is to find disease‐altering treatments and better symptom relief for patients. We present the study design, types of data collected, and characteristics of the first 1150 patients enrolled. We also discuss ongoing analyses on this dataset, including untargeted‐omics methodologies. [ABSTRACT FROM AUTHOR]

Mutations in the Cu/Zn superoxide dismutase (SOD1) gene cause familial amyotrophic lateral sclerosis (FALS) by gain of an aberrant function that is not yet well understood. The role of Cu2+ in mediating the toxicity of mutant SOD1 has been earnestly contested. We tested the in vivo effects of genetically induced copper deprivation on the ALS phenotype of transgenic mice expressing G86R mutant mouse SOD1, a protein that fails to incorporate Cu2+ in its active site. Genetically copper-deficient SOD1G86R transgenic mice were produced by mating SOD1G86R males to female carriers of the X-linked mottled/brindled (Mobr) mutation. We found that the Mobr allele causes a severe (∼ 60%) depletion of spinal cord copper levels; however, despite the burden of double genetic lesions, it lengthens the lives of SOD1G86R transgenic mice by 9%. These findings provide evidence supporting a role for copper in the pathogenesis of FALS linked to SOD1 mutations. [ABSTRACT FROM AUTHOR]

Purpose of Review: Although medication, toxic, and vitamin-related neuropathies are rare causes of neuropathy, they are important to recognize because they are treatable and preventable. It is often difficult to conclusively demonstrate that a particular agent is the cause of neuropathy, but understanding the specific electrodiagnostic and clinical patterns produced by these agents is critical for making these assessments., Recent Findings: The clinical and electrodiagnostic features for many of these neuropathies have been well established. The exact mechanism by which some of these agents produce neuropathy is only now beginning to be revealed. These mechanisms are critical for both understanding the normal function of nerves as well as eventually devising specific treatments., Summary: A large number of medications and toxins can produce neuropathy. This article reviews the clinical characteristics, electrodiagnostic features, and mechanism of action (when known) of those agents that produce the most severe, or perhaps the most unique features of, neuropathy.