Effects of the continuous subcutaneous infusion of foslevodopa-foscarbidopa on swallowing in patients with Parkinson's disease.

Background: Dysphagia is a potentially fatal symptom of Parkinson's disease (PD) and is characterized by frequent silent aspiration, a known risk factor for aspiration pneumonia. A previous study has reported that the dopamine agonist rotigotine (levodopa equivalent dose of 60 mg/day) delivered via transdermal patch improves swallowing function more effectively than oral levodopa (200 mg/day), highlighting the importance of continuous dopaminergic stimulation (CDS) in managing dysphagia. To achieve CDS, patients with advanced PD may require device-assisted therapies (DATs), including levodopa-carbidopa intestinal gel (LCIG), which have significantly improved swallowing function on some measures.

Non-coding repeat analyses in patients with Parkinson's disease.

Introduction: The genetic etiology of Parkinson's disease (PD) is complex; approximately 10% of patients with PD have various gene mutations that lead to familial forms of the disease. Recent analyses of non-coding repeat regions revealed that many neurodegenerative diseases are associated with pathological expansions. We evaluated the genetic background of non-coding repeat expansions in Japanese patients with PD.

Conformational Switch in the Alpha-Synuclein C-Terminal Domain Directs Its Fibril Polymorphs.

α-Synuclein (αSyn) inclusions are a pathological hallmark of several neurodegenerative disorders. While cryo-electron microscopy studies have revealed distinct fibril polymorphs across different synucleinopathies, the molecular switches controlling polymorphism remain unveiled. In this study, we found that fibril morphology is associated with the conformational state of monomeric αSyn.

Dissecting the mechanism of NOP56 GGCCUG repeat-associated non-AUG translation using cell-free translation systems.

The repeat expansion in the human genome contributes to neurodegenerative disorders such as spinocerebellar ataxia (SCA) and amyotrophic lateral sclerosis. Transcripts with repeat expansions undergo noncanonical translation called repeat-associated non-AUG (RAN) translation. The NOP56 gene, implicated in SCA36, contains a GGCCTG repeat in its first intron.

Expanding the Genetic and Clinical Spectrum of -Related Hemiplegic Migraine: Analysis of Mutations in Japanese.

Familial hemiplegic migraine (FHM) is characterized by repeated episodes of reversible localized neurological deficits, in addition to headache. The aura of HM includes visual, sensory, motor, and verbal symptoms. Hemiplegic migraine (HM) is classified into non-familial sporadic HM (SHM) and familial HM (FHM).

TDP-43 transports ferritin heavy chain mRNA to regulate oxidative stress in neuronal axons.

Amyotrophic lateral sclerosis (ALS) is characterized by the mislocalization and abnormal deposition of TAR DNA-binding protein 43 (TDP-43). This protein plays important roles in RNA metabolism and transport in motor neurons and glial cells. In addition, abnormal iron accumulation and oxidative stress are observed in the brain and spinal cord of patients with ALS exhibiting TDP-43 pathology and in animal models of ALS.

L-arginine in patients with spinocerebellar ataxia type 6: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial.

Background: Therapeutic advancements for the polyglutamine diseases, particularly spinocerebellar degeneration, are eagerly awaited. We evaluated the safety, tolerability, and therapeutic effects of L-arginine, which inhibits the conformational change and aggregation of polyglutamine proteins, in patients with spinocerebellar ataxia type 6 (SCA6).

Methods: A multicenter, randomized, double-blind, placebo-controlled phase 2 trial (clinical trial ID: AJA030-002, registration number: jRCT2031200135) was performed on 40 genetically confirmed SCA6 patients enrolled between September 1, 2020, and September 30, 2021.

Role of Lipids in the Pathogenesis of Parkinson's Disease.

Aggregation of α-synuclein (αSyn) and its accumulation as Lewy bodies play a central role in the pathogenesis of Parkinson's disease (PD). However, the mechanism by which αSyn aggregates in the brain remains unclear. Biochemical studies have demonstrated that αSyn interacts with lipids, and these interactions affect the aggregation process of αSyn.

Differentiating multiple sclerosis and neuromyelitis optica spectrum disorders through pontine trigeminal nerve lesions: A comparative MRI study.

Purpose: Multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) are two major demyelinating diseases affecting the central nervous system (CNS). The objective of this study is to evaluate the prevalence of pontine trigeminal nerve lesions in patients diagnosed with MS and NMOSD using MRI.

Methods: This retrospective study included patients diagnosed with MS or NMOSD between July 2018 and July 2023.

Takotsubo cardiomyopathy in Guillain-Barré syndrome.

Background And Purpose: Takotsubo cardiomyopathy (TCM) is a serious autonomic complication of Guillain-Barré syndrome (GBS). However, the association between TCM and GBS has not been investigated in detail. We investigated the characteristics of GBS patients with TCM (GBS-TCM).

eIF5 stimulates the CUG initiation of RAN translation of poly-GA dipeptide repeat protein (DPR) in C9orf72 FTLD/ALS.

Tandem GGGGCC repeat expansion in C9orf72 is a genetic cause of frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). Transcribed repeats are translated into dipeptide repeat proteins via repeat-associated non-AUG (RAN) translation. However, the regulatory mechanism of RAN translation remains unclear.

The effect of rasagiline on swallowing function in Parkinson's disease.

Dysphagia, a potentially fatal symptom of Parkinson's disease, is characterized by frequent silent aspiration, a risk factor for aspiration pneumonia. The transdermal dopamine agonist rotigotine alleviates dysphagia in patients with Parkinson's disease and is more effective than oral levodopa, suggesting the importance of continuous dopaminergic stimulation during swallowing. Rasagiline is a monoamine oxidase B (MAOB) inhibitor that facilitates continuous dopaminergic stimulation.

Reconstitution of C9orf72 GGGGCC repeat-associated non-AUG translation with purified human translation factors.

Nucleotide repeat expansion of GGGGCC (GC) in the non-coding region of C9orf72 is the most common genetic cause underlying amyotrophic lateral sclerosis and frontotemporal dementia. Transcripts harboring this repeat expansion undergo the translation of dipeptide repeats via a non-canonical process known as repeat-associated non-AUG (RAN) translation. In order to ascertain the essential components required for RAN translation, we successfully recapitulated GC-RAN translation using an in vitro reconstituted translation system comprising human factors, namely the human PURE system.

CANVAS-related RFC1 mutations in patients with immune-mediated neuropathy.

Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) has recently been attributed to biallelic repeat expansions in RFC1. More recently, the disease entity has expanded to atypical phenotypes, including chronic neuropathy without cerebellar ataxia or vestibular areflexia. Very recently, RFC1 expansions were found in patients with Sjögren syndrome who had neuropathy that did not respond to immunotherapy.

Memantine administration prevented chorea movement in Huntington's disease: a case report.

Background: Huntington's disease is an autosomal dominant inherited disorder characterized by personality changes (such as irritability and restlessness) and psychotic symptoms (such as hallucinations and delusions). When the personality changes become noticeable, involuntary movements (chorea) also develop. The disease is caused by the CAG repeat expansion in the coding region of the HTT gene, and the diagnosis is based on the presence of this expansion.

The effects of safinamide on dysphagia in Parkinson's disease.

Dysphagia is a potentially fatal symptom of Parkinson's disease (PD) and is characterized by frequent silent aspiration, a risk factor for aspiration pneumonia. The transdermal dopamine agonist rotigotine alleviates dysphagia in patients with PD and is more effective than oral levodopa, suggesting the importance of continuous dopaminergic stimulation (CDS) in swallowing. Safinamide is a monoamine oxidase B (MAOB) inhibitor that facilitates CDS.

A case of thymoma-associated myasthenia gravis accompanied with myositis showing the clusters of histiocyte along the fascicles in perimysium.

Patients with myasthenia gravis (MG) often have other autoimmune disorders. However, the coexistence of MG and myositis is rare. Here, we report a case of a 77-year-old woman who developed mild fatigable muscle weakness and diplopia in 3 months.

Phosphatidylinositol-3,4,5-trisphosphate interacts with alpha-synuclein and initiates its aggregation and formation of Parkinson's disease-related fibril polymorphism.

Lipid interaction with α-synuclein (αSyn) has been long implicated in the pathogenesis of Parkinson's disease (PD). However, it has not been fully determined which lipids are involved in the initiation of αSyn aggregation in PD. Here exploiting genetic understanding associating the loss-of-function mutation in Synaptojanin 1 (SYNJ1), a phosphoinositide phosphatase, with familial PD and analysis of postmortem PD brains, we identified a novel lipid molecule involved in the toxic conversion of αSyn and its relation to PD.

Sustained therapeutic benefits by transient reduction of TDP-43 using ENA-modified antisense oligonucleotides in ALS/FTD mice.

The abnormal aggregation of TDP-43 into cytoplasmic inclusions in affected neurons is a pathological hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Although how TDP-43 forms cytoplasmic aggregates and causes neurodegeneration in patients with ALS/FTD remains unclear, reducing cellular TDP-43 levels is likely to prevent aggregation and to rescue neurons from TDP-43 toxicity. To address this issue, here we developed gapmer-type antisense oligonucleotides (ASOs) against human TDP-43 using 2'-,4'--ethylene nucleic acids (ENAs), which are modified nucleic acids with high stability, and tested the therapeutic potential of lowering TDP-43 levels using ENA-modified ASOs.