Hereditary Neurological Disorders

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.

Heterozygous and Homozygous RFC1 AAGGG Repeat Expansions are Common in Idiopathic Peripheral Neuropathy

The paper identifies RFC1 AAGGG repeat expansions in idiopathic peripheral neuropathy patients using a new computational pipeline and finds both heterozygous and homozygous expansions contribute to the condition.

Multifaceted fusion defects converge on altered mitochondrial distribution and increased mutant mitofusin level in CMT2A models

This study investigates how different CMT2A mutations affect mitochondrial distribution and mutant mitofusin levels in Drosophila models, revealing a spectrum of dominant effects linked to disease severity.

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.

Unraveling the distinct motion bias of TrkA-NGF complex in NGFR100W-driven HSAN V disease

This study uses molecular dynamics simulations to analyze how NGFR100W mutation affects the structural dynamics of the TrkA-NGF complex, revealing altered motion patterns linked to HSAN V disease mechanisms.

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.

Arrayed CRISPR/Cas9 Loss-Of-Function Screen in a Neuronal Model of Adaptor Protein Complex 4 Deficiency Identifies Modulators of ATG9A Trafficking

The paper uses a CRISPR/Cas9 screen to identify genes modulating ATG9A trafficking in a neuronal model of AP-4 deficiency, revealing ANPEP and NPM1 as key regulators.

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.

Multiple roles for TFG ring complexes in neuronal cargo trafficking

This study identifies structural and functional roles of TFG ring complexes in neuronal cargo trafficking, showing how mutations disrupt their stability and contribute to neurodegenerative disease.

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.

Loss of IVNS1ABP, a gigaxonin paralogue, leads to a progeroid neuropathy due to impaired proteostasis

This study shows that loss of IVNS1ABP causes a progeroid neuropathy by impairing proteostasis, leading to protein aggregation and lysosomal dysfunction in neuronal cells.

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.

Genetic Risk of Axonal Neuropathy Following Infection

The paper identifies biallelic RCC1 variants causing an acute axonal neuropathy triggered by infection, with mechanistic overlap with ALS and GBS.

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.

Gigaxonin, mutated in Giant Axonal Neuropathy, interacts with TDP-43 and other RNA binding proteins

This study identifies RNA-binding protein interactions of gigaxonin, a protein mutated in Giant Axonal Neuropathy, revealing potential mechanisms linking its dysfunction to neurodegeneration.

Biallelic variants in COX18 cause a mitochondrial disorder primarily manifesting as peripheral neuropathy

This study identifies biallelic COX18 variants as a cause of autosomal recessive axonal CMT with peripheral neuropathy and potential central nervous system involvement.

Peripheral Neuropathy in the Adreno-myelo-neuropathy Mouse Model

The paper examines peripheral neuropathy in an Abcd1 knockout mouse model, finding normal nerve conduction despite axonal abnormalities.

Biallelic variants in ARHGAP19 cause a motor-predominant neuropathy with asymmetry and conduction slowing

The paper identifies biallelic variants in ARHGAP19 as a cause of motor-predominant neuropathy with conduction slowing in multiple families.

A deep intronic variant in MME causes autosomal recessive Charcot-Marie-Tooth neuropathy through aberrant splicing

The paper identifies a deep intronic MME variant causing CMT through aberrant splicing, highlighting the importance of considering deep intronic variants in CMT diagnosis.

Novel inhibitors of acute, axonal DLK palmitoylation are neuroprotective and avoid the deleterious side effects of cell-wide DLK inhibition

The paper identifies novel compounds that inhibit DLK palmitoylation in axons, providing neuroprotection without causing cytoskeletal disruption seen with broader DLK inhibition.

Characterization of a novel zebrafish model of MTMR5-associated CMT4B3

The paper creates a zebrafish model of CMT4B3 that mirrors human disease features, providing a pre-clinical tool for research and therapy development.

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.

Altered NRG1/ErbB4 signaling and cholesterol metabolism dysregulation are key pathomechanisms in VRK1-related motor neuropathies and motor neuron diseases

The paper investigates VRK1-related motor neuropathies using hiPSC-MNs and bulk mRNA-Seq, identifying altered NRG1/ErbB4 signaling and cholesterol metabolism dysregulation as key pathomechanisms.

Decreasing ganglioside synthesis delays motor and cognitive symptom onset in Spg11 knockout mice

This study shows that reducing ganglioside synthesis delays motor and cognitive symptoms in Spg11 knockout mice and reduces axonal spheroids.

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.