On the other hand, in our experiments, clearly positive reactions for fukutin are observed in a few of these cells (12). The expression is retained in many internal granular layer cells of the adult cerebellum (12, 15). These contradictory findings might be derived from differences in experimental procedures including the probes and antibodies used. However, Inhibitors,research,lifescience,medical it appears that the expression of

fukutin tends to be low after the maturation of neurons in humans, although it depends on the type of neuron. In immunohistochemistry using the antibody for glycosylated α-DG, cerebral cortical neurons and neuropils are negative both in FCMD and control cases from fetuses to adults (Fig. ​(Fig.1).1). With an antibody Inhibitors,research,lifescience,medical for core α-DG, immature neurons of the cerebral cortex and germinal matrix are stained positively, and no apparent difference can be found between fetal FCMD and control cases (Fig. ​(Fig.1).1). α-DG is considered to play a key role for proper proliferation and differentiation in immature neuroepithelial cells (16). Since both

fukutin and α-DG are expressed in immature neurons, fukutin might work via α-DG for the proper development of immature neurons. Heterotopic neurons in the cerebral white Inhibitors,research,lifescience,medical matter of FCMD patients support this speculation. In post-natal FCMD and control cases, neuronal cytoplasm and neuropils give positive reactions with the antibody for core α-DG. More dendrites appear to be stained in FCMD cases. This result appears to be compatible with a post-synaptic role of α-DG (17), but it is unclear whether glycosylated α-DG is required for this function or not. Similarly, there is no clear evidence of how fukutin is involved in the function of mature cerebral cortical neurons at present. On the other hand, altered glycosylation

Inhibitors,research,lifescience,medical of α-DG has been observed in hippocampal neurons of FCMD Inhibitors,research,lifescience,medical (18). With immuhohistochemistry to detect oxidative modification products, there was a slight accumulation of CML in the neurons of a severe 2-year-old case (Fig. ​(Fig.1).1). Although there was no significant CML accumulation in common and mild cases from 14-27 years, there were more positive reactions for Mn superoxide dismutase, an enzyme against oxidative stress existing in mitochondria, compared to controls. In common and mild cases, more active participation of anti-oxidants may prevent the accumulation of CML. Neurons also appear to be sensitive MTMR9 to oxidative stress, and the accumulation of CML may be greater when gene impairment is severe. Future perspectives The selleck characteristics of neurons and astrocytes have gradually been elucidated in the CNS of FCMD. However, there are still many unresolved aspects. Even in neurons, it has still not been proven that fukutin works toward neuronal migration or against it, or has other roles. Increased sensitivity to oxidative stress in astrocytes and neurons may be related to the increase of corpora amylacea and neurofibrillay tangles, but the mechanism is unknown.