Recurrent hypogeusia in a patient with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).

Hypogeusia, a condition with diminished sense of taste, is caused by several conditions, including zinc deficiency and as a side-effect of drugs, but is not common in neurological disorders. A 55-year-old Japanese man with a 30-year history of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) presented with hypogeusia during hospitalization for a recurrence of CIDP. The hypogeusia improved after treatment with high-dose intravenous methylprednisolone (HIMP). Two years later, hypogeusia developed again. A complete taste deficit was revealed by a filter paper test. Brain MRI showed enhancement of the bilateral facial nerve ganglia. Hypogeusia was partially ameliorated after extensive immunosuppressive therapy with repeated HIMP and plasma exchange. Improvement was more prominent in the area innervated by the chorda tympani nerve than that innervated by the glossopharyngeal nerve. To our knowledge, this is the first report of recurrent hypogeusia, which might be caused by cranial nerve injury associated with CIDP.

Histochemical features of stress-induced aggregates in alpha-synuclein overexpressing cells.

alpha-Synuclein is a major component of intracytoplasmic inclusions including Lewy bodies (LB), Lewy neurites (LN) and glial cytoplasmic inclusions, and plays a key role in neurodegenerative processes in Parkinson's disease (PD) and other synucleinopathies. Although the molecular mechanisms of the disease process still remain to be elucidated, recent studies have suggested that an interaction between reactive oxygen species (ROS) and alpha-synuclein may be closely associated with the initiation and/or the progression of synucleinopathies. In this study, we established human dopaminergic SH-SY5Y cell lines overexpressing wild-type or mutant alpha-synuclein and exposed them to various ROS generators. After the exposure to ROS, alpha-synuclein aggregates were formed in the cytoplasm of these cells, and these were immunopositive for ubiquitin, nitrotyrosine and dityrosine, and positive for thioflavin S staining. Thus, the obtained cytoplasmic aggregates shared many features with inclusion bodies in synucleinopathies. The gamma-tubulin and molecular chaperones coexisted as well, suggesting that the aggregate formation is associated with the intracellular transport along microtubules and may reflect protective responses against neuronal insults. This cellular model not only will be informative for our understanding of the pathophysiological process in synucleinopathies, but also can be applied to the screening of neuroprotective molecules with therapeutic potential.

Mutant SOD1 linked to familial amyotrophic lateral sclerosis, but not wild-type SOD1, induces ER stress in COS7 cells and transgenic mice.

Mutations in a Cu, Zn-superoxide dismutase (SOD1) cause motor neuron death in human familial amyotrophic lateral sclerosis (FALS) and its mouse model, suggesting that mutant SOD1 has a toxic effect on motor neurons. However, the question of how the toxic function is gained has not been answered. Here, we report that the mutant SOD1s linked to FALS, but not wild-type SOD1, aggregated in association with the endoplasmic reticulum (ER) and induced ER stress in the cDNA-transfected COS7 cells. These cells showed an aberrant intracellular localization of mitochondria and microtubules, which might lead to a functional disturbance of the cells. Motor neurons of the spinal cord in transgenic mice with a FALS-linked mutant SOD1 also showed a marked increase of GRP78/BiP, an ER-resident chaperone, just before the onset of motor symptoms. These data suggest that ER stress is involved in the pathogenesis of FALS with an SOD1 mutation.