A novel mouse model for investigating α-synuclein aggregates in oligodendrocytes: implications for the glial cytoplasmic inclusions in multiple system atrophy.

The aggregated alpha-synuclein (αsyn) in oligodendrocytes (OLGs) is one of the pathological hallmarks in multiple system atrophy (MSA). We have previously reported that αsyn accumulates not only in neurons but also in OLGs long after the administration of αsyn preformed fibrils (PFFs) in mice. However, detailed spatial and temporal analysis of oligodendroglial αsyn aggregates was technically difficult due to the background neuronal αsyn aggregates.

A RaPID Macrocyclic Peptide That Inhibits the Formation of α-Synuclein Amyloid Fibrils.

There is considerable interest in drug discovery targeting the aggregation of α-synuclein (αSyn) since this molecular process is closely associated with Parkinson's disease. However, inhibiting αSyn aggregation remains a major challenge because of its highly dynamic nature which makes it difficult to form a stable binding complex with a drug molecule. Here, by exploiting Random non-standard Peptides Integrated Discovery (RaPID) system, we identified a macrocyclic peptide, BD1, that could interact with immobilized αSyn and inhibit the formation of fibrils.

Rheumatoid meningitis developed in patient with stable rheumatoid arthritis and myasthenia gravis-detailed analysis of intracranial inflammation using flow cytometry.

Background: Rheumatoid meningitis (RM) is a rare disorder that often develops during a remission phase of rheumatoid arthritis (RA). This is the first study to demonstrate differences in regard to immunological disturbance between blood and cerebrospinal fluid (CSF) samples obtained from a patient with RM using flow cytometry.

Case Presentation: A 36-year-old woman with RA and generalized myasthenia gravis (MG) developed RM during a remission phase.

Severe and prolonged ictal paresis in an elderly patient.

We report an 84-year-old female who showed a rare manifestation of epilepsy, ictal paresis, a type of simple partial seizure presenting with focal motor dysfunction. While the patient exhibited severe left hemiplegia which lasted for a week, cranial diffusion-weighted MRI demonstrated slightly high intensity in the right posterior quadrant, and electroencephalography (EEG) showed continuous epileptiform discharges located mainly in the right parieto-occipital area, strongly suggesting that the patient was in an ictal state. (99m)Tc-hexamethylpropylene amine oxime-single photon emission computed tomography (HMPAO-SPECT) showed markedly high blood perfusion in the right parieto-temporo-occipital areas.

Transglutaminase 2 accelerates neuroinflammation in amyotrophic lateral sclerosis through interaction with misfolded superoxide dismutase 1.

Although the aberrant assembly of mutant superoxide dismutase 1 (mSOD1) is implicated in the pathogenesis of familial amyotrophic lateral sclerosis (ALS), the molecular basis of superoxide dismutase 1 (SOD1) oligomerization remains undetermined. We investigated the roles of transglutaminase 2 (TG2), an endogenous cross-linker in mSOD1-linked ALS. TG2 interacted preferentially with mSOD1 and promoted its oligomerization in transfected cells.

Conserved acidic amino acid residues in a second RNA recognition motif regulate assembly and function of TDP-43.

Accumulating evidence suggests that pathogenic TAR DNA-binding protein (TDP)-43 fragments contain a partial RNA-recognition motif domain 2 (RRM2) in amyotrophic lateral sclerosis (ALS)/frontotemporal lobar degeneration. However, the molecular basis for how this domain links to the conformation and function of TDP-43 is unclear. Previous crystal analyses have documented that the RRM2-DNA complex dimerizes under acidic and high salt conditions, mediated by the intermolecular hydrogen bonds of Glu246-Ile249 and Asp247-Asp247.

Colocalization of 14-3-3 proteins with SOD1 in Lewy body-like hyaline inclusions in familial amyotrophic lateral sclerosis cases and the animal model.

Background And Purpose: Cu/Zn superoxide dismutase (SOD1) is a major component of Lewy body-like hyaline inclusion (LBHI) found in the postmortem tissue of SOD1-linked familial amyotrophic lateral sclerosis (FALS) patients. In our recent studies, 14-3-3 proteins have been found in the ubiquitinated inclusions inside the anterior horn cells of spinal cords with sporadic amyotrophic lateral sclerosis (ALS). To further investigate the role of 14-3-3 proteins in ALS, we performed immunohistochemical analysis of 14-3-3 proteins and compared their distributions with those of SOD1 in FALS patients and SOD1-overexpressing mice.

Induction of protective immunity by vaccination with wild-type apo superoxide dismutase 1 in mutant SOD1 transgenic mice.

Vaccinations targeting extracellular superoxide dismutase 1 (SOD1) mutants are beneficial in mouse models of amyotrophic lateral sclerosis (ALS). Because of its misfolded nature, wild-type nonmetallated SOD1 protein (WT-apo) may have therapeutic application for vaccination of various SOD1 mutants. We compared the effects of WT-apo to those of a G93A SOD1 vaccine in low-copy G93A SOD1 transgenic mice.

[Trial of rituximab in three patients with neuromyelitis optica].

Patients with relapsing neuromyelitis optica (NMO) showing contiguous long spinal cord lesions extending over three vertebral segments on the MRI and with positive anti-aquaporin 4 antibodies in sera are usually treated with glucocorticoids or azathioprine. However, some NMO patients even after adequate treatments show relapses. Rituximab (anti-CD 20) therapy has recently been reported to inhibit relapses.