Hereditary Neurological Disorders

Chronic Proliferation and Glia Heterogeneity in CMT1A: Involvement of RUNX2-Positive Schwann Cells and Endoneurial Fibroblasts

The paper investigates chronic proliferation and glia heterogeneity in CMT1A rat sciatic nerves, identifying RUNX2-positive Schwann cells and endoneurial fibroblasts as key contributors to disease pathology.

Proteomic profiling of Elp1-deficient trigeminal ganglia reveals disruption of neurotrophic and metabolic pathways in a familial dysautonomia mouse model

The paper uses proteomic profiling to identify molecular changes in Elp1-deficient trigeminal ganglia, revealing disruptions in neurotrophic and metabolic pathways in a familial dysautonomia mouse model.

LIS1 is critical for axon integrity in adult mice

This study shows LIS1 depletion in adult mice causes axonal degeneration in projection neurons, suggesting LIS1's role in maintaining axon integrity in mature neurons.

Digenic inheritance of mutations in SPG7 and AFG3L2 causes motor neuron and cerebellar disorders

This study identifies digenic inheritance of SPG7 and AFG3L2 mutations as a cause of motor neuron and cerebellar disorders in 17 patients.

Muscle-specific DNM2 overexpression improves Charcot-Marie-Tooth disease in vivo and reveals a narrow therapeutic window in skeletal muscle

This study shows that muscle-specific DNM2 overexpression improves CMT symptoms in mice, but systemic delivery worsens muscle pathology, highlighting a narrow therapeutic window for DNM2 modulation.

The Charcot-Marie-Tooth Neuropathy (CMTX3) Complex Structural Variation Causes Differential SOX3 Spatiotemporal Expression

The paper identifies a 78-kb insertion in the CMTX3 locus that causes spatiotemporal dysregulation of SOX3 expression in neuronal differentiation.

Aberrant Molecular Myelin Architecture in Charcot-Marie-Tooth Disease Type 1A and Hereditary Neuropathy with Liability to Pressure Palsies

This study identifies molecular myelin architecture disruptions in CMT1A and HNPP models, linking PMP22 dosage to myelin defects and disease pathogenesis.

Loss-of-function Variants in CPT1C: No Support for a Causal Role in Hereditary Spastic Paraplegia

The paper investigates whether CPT1C loss-of-function variants cause hereditary spastic paraplegia (HSP) by analyzing genomic data from multiple cohorts and finds no causal association.

Targeted plasma proteomics uncover novel proteins associated with KIF5A-linked SPG10 and ALS spectrum disorders

This study identifies novel plasma proteins associated with KIF5A-linked SPG10 and ALS using targeted proteomics, revealing distinct proteomic signatures and potential biomarkers.

Novel neurofilament light (Nefl) E397K mouse models of Charcot-Marie-Tooth type 2E (CMT2E) present early and chronic axonal neuropathy

This study creates and characterizes Nefl E397K mouse models of CMT2E, showing early axonal neuropathy and electrophysiological abnormalities.

The NeflE397K mouse model demonstrates muscle pathology and motor function deficits consistent with CMT2E

This paper characterizes motor function deficits, muscle pathology, and breathing abnormalities in NeflE397K mice, showing progressive disease severity with genotype.

PCSK9 deficiency promotes the development of peripheral neuropathy

This study shows that PCSK9 deficiency in mice causes peripheral neuropathy through lipid homeostasis disruption, including reduced Schwann cells and mitochondrial abnormalities.

Neurofilament accumulation disrupts autophagy in giant axonal neuropathy

This paper shows that neurofilament accumulation in GAN disrupts autophagy through impaired organelle distribution and sequestration of 14-3-3, affecting TFEB localization.

A major disease-related point mutation in spastin alters dramatically the dynamics and allostery of the motor

This study uses molecular dynamics and machine learning to analyze how the R591S mutation in spastin affects its dynamics and allostery, leading to impaired microtubule severing and HSP-related dysfunction.

Targeted long-read sequencing as a single assay improves diagnosis of spastic-ataxia disorders

This paper demonstrates that targeted long-read sequencing improves genetic diagnosis of spastic-ataxia disorders by identifying causative variants in 41% of undiagnosed cases using a single assay.

IP3 receptor depletion in a spontaneous canine model of Charcot-Marie-Tooth disease 1J with amelogenesis imperfecta

This paper identifies a homozygous nonsense variant in ITPR3 in Lancashire Heeler dogs causing enamel defects and nerve dysfunction, showing IP3R3 loss affects IP3R1 and IP3R2 levels and Ca2+ signaling.

Activation of XBP1s attenuates disease severity in models of proteotoxic Charcot-Marie-Tooth type 1B

This study shows that activating XBP1s reduces disease severity in CMT1B models by mitigating ER stress and mutant protein toxicity in Schwann cells.

Genipin Crosslinks the Extracellular Matrix to Rescue Developmental and Degenerative Defects, and Accelerates Regeneration of Peripheral Neurons

Genipin rescues developmental and degenerative defects in familial dysautonomia and enhances neuron regeneration after injury.

Axon demyelination and degeneration in a zebrafishspastizin model of hereditary spastic paraplegia

This study investigates the effects of spastizin mutations in zebrafish, showing axon demyelination and degeneration in M-cells, leading to impaired locomotion.

Monitoring myelin lipid composition and structure of myelinated fibers reveals a maturation delay in CMT1A

The paper analyzes myelin lipid composition and structure in CMT1A rats to show delayed maturation of myelin and axon development.

PMP22 associates with MPZ via their transmembrane domains and disrupting this interaction causes a loss-of-function phenotype similar to hereditary neuropathy associated with liability to pressure palsies (HNPP).

This study identifies the molecular interaction between PMP22 and MPZ through their transmembrane domains and shows how disrupting this interaction causes a loss-of-function phenotype in hereditary neuropathy.

Boosting BDNF in muscle rescues impaired axonal transport in a mouse model of DI-CMTC peripheral neuropathy

Sord deficient rats develop a motor-predominant peripheral neuropathy unveiling novel pathophysiological insights

This study generates a Sord knockout rat model to study SORD deficiency, revealing motor-predominant neuropathy with elevated sorbitol and neurofilament light chain levels.

Testing SIPA1L2 as a modifier of CMT1A using mouse models

The paper tests SIPA1L2 as a modifier of CMT1A using mouse models and identifies some genetic interactions but finds a small overall effect on neuropathy.

Transcriptome analysis in a humanized mouse model of familial dysautonomia reveals tissue-specific gene expression disruption in the peripheral nervous system.

This study uses transcriptome analysis in a humanized mouse model of FD to identify tissue-specific gene expression disruptions in the peripheral nervous system.

Structural bases for the Charcot-Marie-Tooth disease induced by single amino acid substitutions of myelin protein zero

The paper investigates how single amino acid substitutions in MPZ's extracellular domain cause Charcot-Marie-Tooth disease by analyzing membrane-stacking activity using a novel nanomyelin system.

Full-length isoform sequencing for resolving the molecular basis of Charcot-Marie-Tooth 2A

The paper uses full-length isoform sequencing to identify a splicing defect in MFN2 causing CMT2A in a patient with undiagnosed neuropathy.

Structural context of homomeric interactions in the Ig domain of the MPZ (P0) myelin adhesion protein and relation to Charcot-Marie-Tooth disease phenotype variants

The paper investigates the structural context of homomeric interactions in the Ig domain of MPZ and their relation to CMT disease phenotypes using NMR and SAXS analysis.

A humanized yeast model reveals dominant-negative properties of neuropathy-associated alanyl-tRNA synthetase mutations

The paper demonstrates that neuropathy-associated AARS1 mutations exhibit dominant-negative effects by reducing yeast growth when co-expressed with wild-type AARS1.

Macrophage depletion blocks congenital SARM1-dependent neuropathy

This study shows that macrophage depletion reverses neuropathic symptoms in a mouse model of SARM1-dependent neuropathy caused by NMNAT2 variants.