Background: Despite advances in reperfusion therapies, ischemic stroke remains a major cause of long-term disability due to residual hypoxic lesions persisting after macrovascular reperfusion. These residual hypoxic lesions, caused by microvascular dysfunction, represent an important therapeutic target. We previously demonstrated that oxygen-glucose-deprived peripheral blood mononuclear cells (OGD-PBMCs) migrate to ischemic brain regions and promote functional recovery after stroke.
View Article and Find Full Text PDFBackground: Progressive supranuclear palsy (PSP) is a major atypical parkinsonism. Because diagnosis based on the cardinal clinical features is often difficult, misdiagnosis with Parkinson's disease (PD) and multiple system atrophy (MSA) is common in PSP patients. Iron metabolism genes are reportedly involved in tau-accumulating neuronal cell death and ferroptosis in PSP, which is more severe than PD and MSA.
View Article and Find Full Text PDFMultiple system atrophy (MSA) is a rare neurodegenerative disease characterized by an accumulation of phosphorylated α-synuclein (p-αsyn) in oligodendrocytes in the form of glial cytoplasmic inclusions (GCIs). In MSA, not only mature oligodendrocytes but also oligodendrocyte precursor cells (OPCs) are affected. The latter play an important role in remyelination by differentiating into mature oligodendrocytes, as well as maintaining the blood-brain barrier (BBB) by promoting the expression of tight junction proteins.
View Article and Find Full Text PDFIntroduction: Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) manifest with variable clinical features. We initiated a multicenter prospective registry study-the Japanese Longitudinal Biomarker Study in PSP and CBD-in November 2014 at 45 Japanese institutions to collect clinical information and biological samples to elucidate the natural courses and diagnostic biomarkers of PSP/CBD.
Methods: Initial symptoms, clinical features, and scores (Progressive Supranuclear Palsy Rating Scale [PSPRS], Barthel Index, Mini-Mental State Examination, and Frontal Assessment Battery) of patients clinically diagnosed with PSP/corticobasal syndrome (CBS) at the first registration were analyzed.
Background: The copy number status (CNS) of the survival motor neuron (SMN) gene may influence the risk and prognosis of amyotrophic lateral sclerosis (ALS) and lower motor neuron diseases (LMND) other than spinal muscular atrophy (SMA). However, previous studies of this association, mainly from Europe, have yielded controversial results, suggesting possible regional differences. Here, we investigated the effect of the SMN gene in Japanese patients with ALS and LMND.
View Article and Find Full Text PDFProgressive multifocal leukoencephalopathy (PML) is a rare central nervous system disease caused by JC virus (JCV) infection. Human immunodeficiency virus (HIV) infection is the greatest risk factor for PML. Other immunological diseases, including systemic sarcoidosis, have also been reported as risk factors for PML.
View Article and Find Full Text PDFBackground: In recent years, cases of dystextia (texting disabilities) and dystypia (typing disabilities) have been reported. However, reports describing isolated dystextia without aphasia or other cognitive impairments are rare, and the detailed pathophysiology is not fully understood. Most Japanese people use the alphabetical spelling system (Romaji) for texting and typing.
View Article and Find Full Text PDFMany RNA-binding proteins (RBPs) are linked to the dysregulation of RNA metabolism in motor neuron diseases (MNDs). However, the molecular mechanisms underlying MN vulnerability have yet to be elucidated. Here, we found that such an RBP, Quaking5 (Qki5), contributes to formation of the MN-specific transcriptome profile, termed "MN-ness," through the posttranscriptional network and maintenance of the mature MNs.
View Article and Find Full Text PDFObjective: Uncoupling protein 2 (UCP2) is an ion/anion transporter in the mitochondrial inner membrane that plays a crucial role in immune response, regulation of oxidative stress, and cellular metabolism. UCP2 polymorphisms are linked to chronic inflammation, obesity, diabetes, heart disease, exercise efficiency, and longevity. Daily step count and number of teeth are modifiable factors that reduce mortality risk, although the role of UCP2 in this mechanism is unknown.
View Article and Find Full Text PDFNeuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease of the CNS characterized by the production of disease-specific autoantibodies against aquaporin-4 (AQP4) water channels. Animal model studies suggest that anti-AQP4 antibodies cause a loss of AQP4-expressing astrocytes, primarily via complement-dependent cytotoxicity. Nonetheless, several aspects of the disease remain unclear, including: how anti-AQP4 antibodies cross the blood-brain barrier from the periphery to the CNS; how NMOSD expands into longitudinally extensive transverse myelitis or optic neuritis; how multiphasic courses occur; and how to prevent attacks without depleting circulating anti-AQP4 antibodies, especially when employing B-cell-depleting therapies.
View Article and Find Full Text PDFBackground: Although cerebral aneurysm (CA) is a defining complication of -related vasculopathy, the specific factors influencing its onset remain uncertain. This study aimed to identify and analyze these factors.
Methods: We described a family presenting with a novel variant of the gene complicated with CA.
The abnormal aggregation of TDP-43 into cytoplasmic inclusions in affected neurons is a major pathological hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Although TDP-43 is aberrantly accumulated in the neurons of most patients with sporadic ALS/FTD and other TDP-43 proteinopathies, how TDP-43 forms cytoplasmic aggregates remains unknown. In this study, we show that a deficiency in DCTN1, a subunit of the microtubule-associated motor protein complex dynactin, perturbs the dynamics of stress granules and drives the formation of TDP-43 cytoplasmic aggregation in cultured cells, leading to the exacerbation of TDP-43 pathology and neurodegeneration in vivo.
View Article and Find Full Text PDFIntroduction: The King's Parkinson's Disease Pain Scale (KPPS)/King's Parkinson's Disease Pain Questionnaire (KPPQ) was developed as a tool to quantitatively assess pain in patients with Parkinson's disease (PwPD). Here, we conducted a Japanese multicenter validation study to verify the reliability of KPPS/KPPQ in Japanese PwPD.
Methods: PwPD, ≥20 years, with unexplained pain were included; those with a definitive primary cause of pain other than PD were excluded.
Background: Metformin (MET) treatment prior to stroke might have neuroprotective effects other than hypoglycemic effects. This study evaluated whether MET treatment prior to stroke is associated with neurological severity and functional outcome in patients with stroke who were not indicated for endovascular treatment and whether the effects of MET differ for each ischemic stroke subtype.
Methods: We investigated 160 type 2 diabetes mellitus patients with ischemic stroke without endovascular treatment who were taking some oral antidiabetic agents prior to stroke in two tertiary hospitals.