BACKGROUND: Mitochondria, which harbor their own genome (mtDNA), have attracted attention due to the potential of mtDNA copy number (mtDNA-CN) as an indicator of mitochondrial dysfunction. Although mtDNA-CN has been proposed as a simple and accessible biomarker for metabolic disorders such as metabolic dysfunction-associated steatotic liver disease, the underlying mechanisms and the causal relationship remain insufficiently elucidated. In this investigation, we combined longitudinal epidemiological data, animal studies, and in vitro assays to elucidate the potential causal relationship between reduced mtDNA-CN and the development of steatotic liver disease (SLD). METHODS: We conducted a longitudinal study using data from a health examination cohort initiated in 1981 in Yakumo, Hokkaido, Japan. Data from examinations performed in 2015 and 2022 were analyzed, focusing on 76 subjects without SLD at baseline (2015) to assess the association between baseline mtDNA-CN and subsequent risk of SLD development. In addition, 28-day-old SD rats were fed ad libitum on a 45% high-fat diet and dissected at 2 and 8 weeks of age. Blood and liver mtDNA-CN were measured and compared at each feeding period. Additionally, in vitro experiments were performed using HepG2 cells treated with mitochondrial function inhibitors to induce mtDNA-CN depletion and to examine its impact on intracellular lipid accumulation. RESULTS: Epidemiological analysis showed that the subjects with low mtDNA-CN had a significantly higher odds ratio for developing SLD compared to high (odds ratio [95% confidence interval]: 4.93 [1.08-22.50]). Analysis of the animal model showed that 8 weeks of high-fat diet led to the development of fatty liver and a significant decrease in mtDNA-CN. A further 2 weeks of high-fat diet consumption resulted in a significant decrease in hepatic mtDNA-CN, despite the absence of fatty liver development, and a similar trend was observed for blood. Complementary in vitro experiments revealed that pharmacologically induced mitochondrial dysfunction led to a significant reduction in mtDNA-CN and was associated with increases in intracellular lipid accumulation in HepG2 cells. CONCLUSIONS Our findings suggest that reduced mtDNA-CN may contribute causally to SLD development and could serve as a convenient, noninvasive biomarker for early detection and risk assessment.
Animals ; DNA, Mitochondrial/genetics* ; Humans ; Male ; DNA Copy Number Variations ; Female ; Fatty Liver/blood* ; Rats ; Middle Aged ; Longitudinal Studies ; Rats, Sprague-Dawley ; Adult ; Japan/epidemiology* ; Aged ; Biomarkers/blood* ; Hep G2 Cells ; Diet, High-Fat/adverse effects*

Mutations in the SNCA gene, which encodes α-synuclein (α-syn), play a key role in the development of genetic Parkinson’s disease (PD). α-Syn is a major component of Lewy bodies in PD and glial cytoplasmic inclusions in multiple system atrophy (MSA). Rapid eye movement sleep behavior disorder patients often progress to PD, dementia with Lewy bodies, or MSA, which are collectively known as α-synucleinopathies. The loss of dopaminergic neurons with Lewy bodies precedes motor dysfunction in these diseases, but the mechanisms of neurodegeneration due to α-syn aggregation are poorly understood. Monitoring α-syn aggregation in vivo could serve as a diagnostic biomarker and help elucidate pathogenesis, necessitating a simple and accurate detection method. Seed amplification assays (SAAs), such as real-time quaking-induced conversion and protein misfolding cyclic amplification, are used to detect small amounts of abnormally structured α-syn protofibrils, which are central to aggregation. These methods are promising for the early diagnosis of α-synucleinopathy. Differences in α-syn filament structures between α-synucleinopathies, as observed through transmission electron microscopy and cryo-electron microscopy, suggest their role in the pathogenesis of neurodegeneration. SAAs may differentiate between subtypes of α-synucleinopathy and other diseases. Efforts are also being made to identify α-syn from blood using various methods. This review introduces body fluid α-syn biomarkers based on pathogenic α-syn seeds, which are expected to redefine α-synucleinopathy diagnosis and staging, improving clinical research accuracy and facilitating biomarker development.

Clinical case studies and reporting are important to the discovery of new disorders and the advancement of medical sciences. Both clinicians and basic scientists play equally important roles leading to treatment discoveries for both cures and symptoms. In the field of movement disorders, exceptional observation of patients from clinicians is imperative, not just for phenomenology but also for the variable occurrences of these disorders, along with other signs and symptoms, throughout the day and the disease course. The Movement Disorders in Asia Task Force (TF) was formed to help enhance and promote collaboration and research on movement disorders within the region. As a start, the TF has reviewed the original studies of the movement disorders that were preliminarily described in the region. These include nine disorders that were first described in Asia: Segawa disease, PARK-Parkin, X-linked dystonia-parkinsonism, dentatorubral-pallidoluysian atrophy, Woodhouse-Sakati syndrome, benign adult familial myoclonic epilepsy, Kufor-Rakeb disease, tremulous dystonia associated with mutation of the calmodulin-binding transcription activator 2 gene, and paroxysmal kinesigenic dyskinesia. We hope that the information provided will honor the original researchers and help us learn and understand how earlier neurologists and basic scientists together discovered new disorders and made advances in the field, which impact us all to this day.

Objective: Using telemedicine is a way to improve the accessibility of specialists for patients with Parkinson’s disease (PD); however, it is not widely used in Japan. We investigated the efficacy of telemedicine in PD by using a single-center cross-sectional questionnaire survey. Methods: We sent a questionnaire to patients who agreed to participate from among 52 patients with PD who had used telemedicine services at Juntendo University Hospital from October 2017 to November 2018. Caregivers were asked to respond to one question separately. Results: A total of 38 patients responded to the questionnaire. Most patients were satisfied with the telemedicine consultation (7.8 ± 1.9), reporting that it was effective in reducing their travel burden. Twenty-one patients attended a telemedicine consultation with their caregivers, and their satisfaction was high (8.4 ± 1.8). Conclusion In a specific cohort in Japan, patients with PD and their caregivers were mostly satisfied with the telemedicine service.

Objective: The long-term efficacy of deep brain stimulation (DBS) for motor fluctuations in advanced Parkinson’s disease (PD) has been well established; however, motor fluctuations may recur over time despite multiple adjustments of DBS settings and medications. Methods: We conducted a retrospective chart review of three patients for whom levodopa-carbidopa intestinal gel (LCIG) was additionally administered as a rescue therapy for secondary DBS failure due to the recurrence of motor fluctuations. Results: The three patients had advanced PD with a disease duration of 14–19 years, and had undergone DBS for motor fluctuations refractory to standard medical management. LCIG was administered to the patients because of symptom recurrence years after DBS and provided complementary effects in all patients. Conclusion The cases presented here show that rescue LCIG therapy may be a complementary treatment option for patients with post-DBS advanced PD who have a recurrence of troublesome motor complications.

Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease, characterized by increasingly morbid motor dysfunction with advancing age. Recently, various antiparkinsonian agents and surgical intervention have been developed that, when used in combination, greatly promote sustained improvements in activities of daily living, leading to the establishment of a treatment algorithm. However, since all of these interventions are symptomatic therapies, it is difficult to resolve motor dysfunction completely. Recent evidence has revealed that exercise might enhance neuroplasticity and improve motor and cognitive behavioral impairment in PD. In this article, we reviewed recent therapeutic strategies for PD.