IκB kinase phosphorylates cytoplasmic TDP-43 and promotes its proteasome degradation.

Cytoplasmic aggregation of TDP-43 in neurons is a pathological feature common to amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). We demonstrate that the IκB kinase (IKK) complex promotes the degradation of cytoplasmic TDP-43 through proteasomes. While IKKβ is a major factor in TDP-43 degradation, IKKα acts as a cofactor, and NEMO functions as a scaffold for the recruitment of TDP-43 to the IKK complex.

Targeting aberrant dendritic integration to treat cognitive comorbidities of epilepsy.

Memory deficits are a debilitating symptom of epilepsy, but little is known about mechanisms underlying cognitive deficits. Here, we describe a Na+ channel-dependent mechanism underlying altered hippocampal dendritic integration, degraded place coding and deficits in spatial memory. Two-photon glutamate uncaging experiments revealed a marked increase in the fraction of hippocampal first-order CA1 pyramidal cell dendrites capable of generating dendritic spikes in the kainate model of chronic epilepsy.

[A case of transient global amnesia associated with painless myocardial infarction].

A 66-year-old woman with a history of hypertension complained about sudden short-term memory loss. On arrival to our outpatient clinic, she was alert and oriented and did not have chest pain or shortness of breath. Neurological and neuropsychological examinations were within normal limits.

Rotatory Vertigo Caused by a Small Hemorrhage in the Superior Temporal Gyrus.

Rotatory vertigo is known to have not only peripheral causes, e.g., Meniere's disease, vestibular neuritis, and benign paroxysmal positional vertigo, but also central causes, e.

Pharmacological monitoring of antiepileptic drugs in epilepsy patients on haemodialysis.

To retrospectively evaluate the pharmacological profiles of antiepileptic drugs (AEDs) in epilepsy patients during haemodialysis using therapeutic drug monitoring data. The serum concentration of AEDs was collected before and after haemodialysis, and the clearance rate and concentration-to-dose ratio were calculated as pharmacological parameters. Thirty-six patients were enrolled in the study (25 males, 11 females; age: 65.

TDP-43 regulates early-phase insulin secretion via CaV1.2-mediated exocytosis in islets.

TAR DNA-binding protein 43 kDa (TDP-43), encoded by TARDBP, is an RNA-binding protein, the nuclear depletion of which is the histopathological hallmark of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disorder affecting both upper and lower motor neurons. Besides motor symptoms, patients with ALS often develop nonneuronal signs including glucose intolerance, but the underlying pathomechanism is still controversial, i.e.

Acute Unilateral Isolated Oculomotor Nerve Palsy in an Adult Patient with Influenza A.

An otherwise healthy 44-year-old woman exhibited isolated unilateral oculomotor nerve palsy accompanied by an influenza A infection. An intra-orbital MRI scan revealed that her right third intracranial nerve was enlarged and enhanced. She recovered completely during the first month after treatment with oseltamivir phosphate.

Clinicopathological features of adult-onset neuronal intranuclear inclusion disease.

Neuronal intranuclear inclusion disease (NIID) is a slowly progressive neurodegenerative disease characterized by eosinophilic hyaline intranuclear inclusions in the central and peripheral nervous system, and also in the visceral organs. NIID has been considered to be a heterogeneous disease because of the highly variable clinical manifestations, and ante-mortem diagnosis has been difficult. However, since we reported the usefulness of skin biopsy for the diagnosis of NIID, the number of NIID diagnoses has increased, in particular adult-onset NIID.

Memory Loss and Frontal Cognitive Dysfunction in a Patient with Adult-onset Neuronal Intranuclear Inclusion Disease.

Neuronal intranuclear inclusion disease (NIID) is an uncommon progressive neurodegenerative disorder. Adult-onset NIID can result in prominent dementia. We herein describe the case of a 74-year-old man who presented with dementia, cerebellar ataxia, neuropathy, and autonomic dysfunction.

Progressive supranuclear palsy and Parkinson's disease overlap: A clinicopathological case report.

We describe a woman with a 13-year history of postural instability, vertical gaze palsy and dopa-responsive parkinsonism - a clinical profile that corresponds to progressive supranuclear palsy (PSP) and Parkinson's disease (PD). The patient died at the age of 82 years. Neuropathological features included neuronal loss and gliosis in the substantia nigra, locus ceruleus, dorsal motor nucleus of the vagus, thoracic intermediolateral nucleus and nucleus basalis of Meynert, in addition to the typical pathology of PSP.

Myotonia-like symptoms in a patient with spinal and bulbar muscular atrophy.

We describe the case of a 33-year-old man with a 4-year history of worsening muscle stiffness and weakness in his right hand. He showed elevated serum creatine kinase levels at the onset of muscle stiffness that was characterized by delayed muscle relaxation after voluntary contraction. This symptom often occurred during cold exposure, and was partially attenuated by sodium channel blockade.

Bidirectional neural connectivity between basal temporal and posterior language areas in humans.

Objective: The basal temporal language area (BTL) is known to be involved in the semantic processing of language. To investigate the neural connectivity between BTL and the posterior language area (PL), we used cortico-cortical evoked potential (CCEP) technique.

Methods: Four patients with intractable epilepsy who underwent presurgical evaluation with subdural electrodes were examined.

Extensive cortical spongiform changes with cerebellar small amyloid plaques: the clinicopathological case of MV2K+C subtype in Creutzfeldt-Jakob disease.

We report a clinical case report of the MV2K+C subtype of sporadic Creutzfeldt-Jakob disease (sCJD). The patient was a 72-year-old woman who exhibited progressive dementia over the course of 22 months. Diffusion-weighted MRI during this period showed abnormal hyperintensity in the cerebral cortex in the early stage.

Mesial temporal lobe epilepsy with no specific histological abnormality: a distinct surgically remediable syndrome.

Purpose: The purposes of the study were twofold: to clarify the clinical features and surgical outcome of mesial temporal lobe epilepsy (MTLE) with no specific histological abnormality and to determine the optimal surgical strategy.

Methods: Twelve patients who met the following criteria were included: (1) normal preoperative MRI; (2) intracranial EEG findings consistent with mesial temporal onset of seizures; (3) selective amygdalohippocampectomy (AHE) was performed, and the patient was followed for more than 2years postoperatively; and (4) hippocampal histopathology was nonspecific. Clinical characteristics, intracranial EEG findings, and postoperative seizure outcome were examined.

Interaction of Rab3B with microtubule-binding protein Gas8 in NIH 3T3 cells.

Rab3 subfamily small G proteins (Rab3A, Rab3B, Rab3C, and Rab3D) control the regulated exocytosis in neuronal/secretory cells. Rab3B is also detected and upregulated in non-neuronal/non-secretory cells, whereas its function remains elusive. In the present study, we identified growth-arrest-specific gene 8 (Gas8), an evolutionally conserved microtubule-binding protein that is upregulated in growth-arrested NIH 3T3 cells and involved in the dynein motor regulation in flagellar/ciliary axoneme, as a novel Rab3B-binding protein using a yeast two-hybrid system.