Much More Than a Scaffold: Cytoskeletal Proteins in Neurological Disorders

Muñoz-Lasso, Diana C.; Romá‐Mateo, Carlos; Pallardó, Federico V.; González-Cabo, Pilar

doi:10.3390/cells9020358

Cited by 91 publications

(81 citation statements)

References 291 publications

(327 reference statements)

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“…Cytoskeletal reorganization is required for neuronal homeostasis and plasticity, and for responses to axon injury and degeneration 63 . Disrupted post-translational modification of neurofilament proteins have been linked to neurodegenerative disorders, including PD 64,65 .…”

Section: Discussionmentioning

confidence: 99%

Functional and molecular early enteric biomarkers for Parkinson’s disease in mice and men

Gries

Christmann

Schulte

et al. 2020

Preprint

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Parkinson's disease (PD) usually has a late clinical onset. The lack of early biomarkers for the disease represents a major challenge for developing timely treatment interventions. Here, we use an -synuclein-overexpressing transgenic (Th-1-SNCA-A30P) mouse model of PD to identify appropriate candidate markers in the gut for early stages of PD before hallmark symptoms begin to manifest. A30P mice did not show alterations in gait parameters at 2 months of age, and these mice were therefore defined as pre-symptomatic A30P mice (psA30P). We discovered early functional motility changes in the gut and early molecular dysregulations in the myenteric plexus of psA30P mice by comparative protein and miRNA profiling and cell culture experiments. We found that the proteins neurofilament light chain, vesicle-associated membrane protein 2 and calbindin 2, together with the miRNAs that regulate them, are potential biomarkers of early PD that may facilitate timely treatment and/or prevention of PD in men.

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Section: Discussionmentioning

confidence: 99%

Functional and molecular early enteric biomarkers for Parkinson’s disease in mice and men

Gries

Christmann

Schulte

et al. 2020

Preprint

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“…Microtubules establish the polarized architecture of neurons and serve as tracks for microtubule motor proteins as they carry proteins and lipids to where they are needed for proper neuronal function. Thus, defects in microtubule dynamics and organization underly a wide array of neurological and neuropsychiatric disorders (Matamoros & Baas, 2016; Muñoz-Lasso, Romá-Mateo, Pallardó, & Gonzalez-Cabo, 2020; Sleigh, Rossor, Fellows, Tosolini, & Schiavo, 2019).…”

Section: Discussionmentioning

confidence: 99%

Whole exome sequencing identifies novel DYT1 dystonia-associated genome variants as potential disease modifiers

Hu¹,

Luxton²,

Lee³

et al. 2020

Preprint

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AbstractBackgroundDYT1 dystonia is a neurological movement disorder characterized by painful sustained muscle contractions resulting in abnormal twisting and postures. In a subset of patients, it is caused by a loss-of-function mutation (ΔE302/303; or ΔE) in the luminal ATPases associated with various cellular activities (AAA+) protein torsinA encoded by the TOR1A gene. The low penetrance of the ΔE mutation (∼30-40%) suggests the existence of unknown genetic modifiers of DYT1 dystonia.MethodsTo identify these modifiers, we performed whole exome sequencing of blood leukocyte DNA isolated from two DYT1 dystonia patients, three asymptomatic carriers of the ΔE mutation, and an unaffected adult relative.ResultsA total of 264 DYT1 dystonia-associated variants (DYT1 variants) were identified in 195 genes. Consistent with the emerging view of torsinA as an important regulator of the cytoskeleton, endoplasmic reticulum homeostasis, and lipid metabolism, we found DYT1 variants in genes that encode proteins implicated in these processes. Moreover, 40 DYT1 variants were detected in 32 genes associated with neuromuscular and neuropsychiatric disorders.ConclusionThe DYT1 variants described in this work represent exciting new targets for future studies designed to increase our understanding of the pathophysiology and pathogenesis of DYT1 dystonia.

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Section: Dyt1 Variants and The Cytoskeletonmentioning

confidence: 99%

Whole exome sequencing identifies novel DYT1 dystonia-associated genome variants as potential disease modifiers

Luxton

Lee

et al. 2020

Preprint

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Background：DYT1 dystonia is a neurological movement disorder characterized by painful sustained muscle contractions resulting in abnormal twisting and postures. In a subset of patients, it is caused by a loss-of-function mutation (ΔE302/303; or ΔE) in the luminal ATPases associated with various cellular activities (AAA+) protein torsinA encoded by the TOR1A gene. The low penetrance of the ΔE mutation (~30-40%) suggests the existence of unknown genetic modifiers of DYT1 dystonia. Results：To identify these modifiers, we performed whole exome sequencing (WES) of blood leukocyte DNA isolated from two DYT1 dystonia patients, three asymptomatic carriers of the ΔE mutation, and an unaffected adult relative. A total of 264 DYT1 dystonia-associated variants (DYT1 variants) were identified in 195 genes. Consistent with the emerging view of torsinA as an important regulator of the cytoskeleton, endoplasmic reticulum homeostasis, and lipid metabolism, we found DYT1 variants in genes that encode proteins implicated in these processes. Moreover, 40 DYT1 variants were detected in 32 genes associated with neuromuscular and neuropsychiatric disorders. Conclusion： The DYT1 variants described in this work represent exciting new targets for future studies designed to increase our understanding of the pathophysiology and pathogenesis of DYT1 dystonia.

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Much More Than a Scaffold: Cytoskeletal Proteins in Neurological Disorders

Cited by 91 publications

References 291 publications

Functional and molecular early enteric biomarkers for Parkinson’s disease in mice and men

Functional and molecular early enteric biomarkers for Parkinson’s disease in mice and men

Whole exome sequencing identifies novel DYT1 dystonia-associated genome variants as potential disease modifiers

Whole exome sequencing identifies novel DYT1 dystonia-associated genome variants as potential disease modifiers

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