A dominant negative Kcnd3 F227del mutation in mice causes spinocerebellar ataxia type 22 (SCA22) by impairing ER and Golgi functioning.

Spinocerebellar ataxia type 22 (SCA22) caused by KCND3 mutations is an autosomal dominant disorder. We established a mouse model carrying the Kcnd3 F227del mutation to study the molecular pathogenesis. Four findings were pinpointed.

MRl and MRS hints for the differentiation of cerebellar multiple system atrophy from spinocerebellar ataxia type II.

Background And Objectives: The differentiation of spinocerebellar ataxia type II (SCA 2) from idiopathic multiple systemic atrophy of the cerebellar type (MSA-C) is often difficult in patients with cerebellar ataxia when molecular testing is not available. Besides genetic testing, magnetic resonance imagining (MRI) and magnetic resonance spectroscopy (MRS) prove to be beneficial. Nevertheless, the characteristics observed through radiology change as the disease advances.

COQ2 and SNCA polymorphisms interact with environmental factors to modulate the risk of multiple system atrophy and subtype disposition.

Background And Purpose: Multiple system atrophy (MSA) has no definitive genetic or environmental (G-E) risk factors, and the integrated effect of these factors on MSA etiology remains unknown. This study was undertaken to investigate the integrated effect of G-E factors associated with MSA and its subtypes, MSA-P and MSA-C.

Methods: A consecutive case-control study was conducted at two medical centers, and the interactions between genotypes of five previously reported susceptible single nucleotide polymorphisms (SNPs; SNCA_rs3857059, SNCA_rs11931074, COQ2_rs148156462, EDN1_rs16872704, MAPT_rs9303521) and graded exposure (never, ever, current) of four environmental factors (smoking, alcohol, drinking well water, pesticide exposure) were analyzed by a stepwise logistic regression model.

Radiological hints for differentiation of cerebellar multiple system atrophy from spinocerebellar ataxia.

Differentiation cerebellar multiple systemic atrophy (MSA-C) from spinocerebellar ataxia (SCA) is important. The "hot cross bun" sign (HCBS) at pons and magnetic resonance spectroscopy (MRS) are helpful. However, the prevalence of HCBS and the alteration of cerebellar MRS parameters are evolving with disease progression.

A PIAS1 Protective Variant S510G Delays polyQ Disease Onset by Modifying Protein Homeostasis.

Background: Polyglutamine (polyQ) diseases are dominant neurodegenerative diseases caused by an expansion of the polyQ-encoding CAG repeats in the disease-causing gene. The length of the CAG repeats is the major determiner of the age at onset (AO) of polyQ diseases, including Huntington's disease (HD) and spinocerebellar ataxia type 3 (SCA3).

Objective: We set out to identify common genetic variant(s) that may affect the AO of polyQ diseases.

Rare Gain-of-Function Variant Associated with Cerebellar Ataxia, Parkinsonism, Cognitive Dysfunction, and Brain Iron Accumulation.

Loss-of-function mutations in the K4.3 channel-encoding gene are linked to neurodegenerative cerebellar ataxia. Patients suffering from neurodegeneration associated with iron deposition may also present with cerebellar ataxia.

Expanding the phenotype of AFG3L2 mutations: Late-onset autosomal recessive spinocerebellar ataxia.

The AFG3L2 gene encodes AFG3-like protein 2, which is a subunit of human mitochondrial ATPases associated with various cellular protease activities (m-AAA). The clinical spectrum of AFG3L2 mutations is broad. Dominant AFG3L2 mutations can cause autosomal dominant spinocerebellar ataxia type 28 (SCA28), whereas biallelic AFG3L2 mutations may lead to spastic ataxia 5 (SPAX5).

Novel Variant Underlying Nonprogressive Congenital Ataxia or SCA19/22 Disrupt K4.3 Protein Expression and K+ Currents with Variable Effects on Channel Properties.

encodes the voltage-gated potassium channel K4.3 that is highly expressed in the cerebellum, where it regulates dendritic excitability and calcium influx. Loss-of-function K4.

Clinical and genetic characterization of hereditary spastic paraplegia type 3A in Taiwan.

Aim: To investigate the clinical and genetic features of hereditary spastic paraplegia (HSP) type 3A (SPG3A) in Taiwan.

Methods: Mutational analysis of the ATL1 gene was performed for 274 unrelated Taiwanese HSP patients. The diagnosis of SPG3A was ascertained by the presence of a heterozygous pathogenic mutation in ATL1.

Investigating CAG/CAA trinucleotide repeat expansions in a Taiwanese cohort with ALS.

Intermediate-length CAG repeats in have been well recognized as a genetic risk factor for amyotrophic lateral sclerosis (ALS). However, the role of similar trinucleotide repeat expansions in the TATA-box binding protein gene (), another disease-associated gene for inherited ataxia, in ALS remains elusive. To assess the association between trinucleotide repeat expansions and ALS, we investigated the repeat lengths in 325 unrelated ALS patients and 1500 controls in the Taiwanese population.

Medical and Paramedical Care of Patients With Cerebellar Ataxia During the COVID-19 Outbreak: Seven Practical Recommendations of the COVID 19 Cerebellum Task Force.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), the cause of the current pandemic coronavirus disease 2019 (COVID-19), primarily targets the respiratory system. Some patients also experience neurological signs and symptoms ranging from anosmia, ageusia, headache, nausea, and vomiting to confusion, encephalitis, and stroke. Approximately 36% of those with severe COVID-19 experience neurological complications.

Management of Patients with Cerebellar Ataxia During the COVID-19 Pandemic: Current Concerns and Future Implications.

The current worldwide severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic that causes coronavirus disease 2019 (COVID-19) has brought some medical systems to the brink of collapse. This crisis is also negatively impacting the care of patients with non-COVID-19 conditions, including those with cerebellar ataxia (CA). Older patients with CA and those with immune-mediated ataxias on immunosuppressive medication are potentially at high risk of developing serious complications of the infection, although it is also possible that immunosuppressive agents may provide a defense against cytokine storm.

Clinical and Genetic Characterization of Autosomal Recessive Spinocerebellar Ataxia Type 16 (SCAR16) in Taiwan.

Mutations in STUB1 have been identified to cause autosomal recessive spinocerebellar ataxia type 16 (SCAR16), also named as Gordon Holmes syndrome, which is characterized by cerebellar ataxia, cognitive decline, and hypogonadism. Additionally, several heterozygous mutations in STUB1 have recently been described as a cause of autosomal dominant spinocerebellar ataxia type 48. STUB1 encodes C-terminus of HSC70-interacting protein (CHIP), which functions as an E3 ubiquitin ligase and co-chaperone and has been implicated in several neurodegenerative diseases.

Clinical characteristics of Taiwanese patients with Hereditary spastic paraplegia type 5.

Objectives: To investigate the clinical, electrophysiological, neuroimaging characteristics and genetic features of SPG5 in Taiwan.

Methods: Mutational analysis of the coding regions of CYP7B1 was performed by utilizing targeted resequencing analysis of the 187 unrelated Taiwanese HSP patients. The diagnosis of SPG5 was ascertained by the presence of biallelic CYP7B1 mutations.

Supratentorial and Infratentorial Lesions in Spinocerebellar Ataxia Type 3.

Spinocerebellar ataxia type 3 (SCA) is a cerebellum-dominant degenerative disorder that is characterized primarily by infratentorial damage, although less severe supratentorial involvement may contribute to the clinical manifestation. These impairments may result from the efferent loss of the cerebellar cortex and degeneration of the cerebral cortex. We used the three-dimensional fractal dimension (3D-FD) method to quantify the morphological changes in the supratentorial regions and assessed atrophy in the relatively focal regions in patients with SCA3.

Diffusion Tensor Magnetic Resonance Imaging for Differentiating Multiple System Atrophy Cerebellar Type and Spinocerebellar Ataxia Type 3.

Multiple system atrophy cerebellar type (MSA-C) and spinocerebellar ataxia type 3 (SCA3) demonstrate similar manifestations, including ataxia, pyramidal and extrapyramidal signs, as well as atrophy and signal intensity changes in the cerebellum and brainstem. MSA-C and SCA3 cannot be clinically differentiated through T1-weighted magnetic resonance imaging (MRI) alone; therefore, clinical consensus criteria and genetic testing are also required. Here, we used diffusion tensor imaging (DTI) to measure water molecular diffusion of white matter and investigate the difference between MSA-C and SCA3.

Xenografting of human umbilical mesenchymal stem cells from Wharton's jelly ameliorates mouse spinocerebellar ataxia type 1.

Background: Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative disorder caused by the expansion of CAG repeats in gene resulting in an expansion of polyglutamine repeats in the ATXN1 protein. Unfortunately, there has yet been any effective treatment so far for SCA1. This study investigated the feasibility of transplanting human umbilical mesenchymal stem cells (HUMSCs) into transgenic SCA1 mice containing an expanded uninterrupted allele with 82 repeats in the coding region.

Investigating PUM1 mutations in a Taiwanese cohort with cerebellar ataxia.

Introduction: Mutations in the PUM1 gene were recently identified to cause spinocerebellar ataxia type 47 (SCA47). However, their role in cerebellar ataxia in various populations remains elusive. The aim of this study was to elucidate the frequency and spectrum of PUM1 mutations in a cohort of Taiwanese patients with molecularly undetermined cerebellar ataxia.

Galectin-3 is required for the microglia-mediated brain inflammation in a model of Huntington's disease.

Huntington's disease (HD) is a neurodegenerative disorder that manifests with movement dysfunction. The expression of mutant Huntingtin (mHTT) disrupts the functions of brain cells. Galectin-3 (Gal3) is a lectin that has not been extensively explored in brain diseases.

Novel SCA19/22-associated KCND3 mutations disrupt human K 4.3 protein biosynthesis and channel gating.

Mutations in the human voltage-gated K channel subunit K 4.3-encoding KCND3 gene have been associated with the autosomal dominant neurodegenerative disorder spinocerebellar ataxia types 19 and 22 (SCA19/22). The precise pathophysiology underlying the dominant inheritance pattern of SCA19/22 remains elusive.

Treadmill training increases the motor activity and neuron survival of the cerebellum in a mouse model of spinocerebellar ataxia type 1.

Spinocerebellar ataxia (SCA) type 1 (SCA1) is a rare autosomal dominant disorder that is characterized by worsening of disordered coordination, ataxia of the trunk, and other neurological symptoms. Physical activity improves both mobility and the daily living activities of patients with SCA. Intervention with daily regular treadmill exercise may slow the deterioration of cerebellar neurons in SCA1.

Intra- and Inter-Modular Connectivity Alterations in the Brain Structural Network of Spinocerebellar Ataxia Type 3.

In addition to cerebellar degeneration symptoms, patients with spinocerebellar ataxia type 3 (SCA3) exhibit extensive involvements with damage in the prefrontal cortex. A network model has been proposed for investigating the structural organization and functional mechanisms of clinical brain disorders. For neural degenerative diseases, a cortical feature-based structural connectivity network can locate cortical atrophied regions and indicate how their connectivity and functions may change.

Modeling spinocerebellar ataxias 2 and 3 with iPSCs reveals a role for glutamate in disease pathology.

Spinocerebellar ataxias 2 and 3 (SCA2 and SCA3) are dominantly inherited neurodegenerative diseases caused by expansion of polyglutamine-encoding CAG repeats in the affected genes. The etiology of these disorders is known to involve widespread loss of neuronal cells in the cerebellum, however, the mechanisms that contribute to cell death are still elusive. Here we established SCA2 and SCA3 induced pluripotent stem cells (iPSCs) and demonstrated that SCA-associated pathological features can be recapitulated in SCA-iPSC-derived neurons.