Fabry disease-associated globotriaosylceramide induces mechanical allodynia via activation of signaling through proNGF-p75 but not mature NGF-TrkA.

Fabry disease (FD) is an X-linked metabolic storage disorder arising from the deficiency of lysosomal α-galactosidase A, which leads to the gradual accumulation of glycosphingolipids, mainly globotriaosylceramide (Gb3), throughout the body. Pain in the extremities is an early symptom of FD; however, the underlying pathophysiological mechanisms remain unknown. α-Galactosidase A knockout animals exhibit nociceptive behaviors, with enhanced expression levels of several ion channels.

Selegiline Recovers Synaptic Plasticity in the Medial Prefrontal Cortex and Improves Corresponding Depression-Like Behavior in a Mouse Model of Parkinson's Disease.

In patients with Parkinson's disease (PD), non-motor symptoms (NMS) including depression and anxiety are often recognized before motor symptoms develop. Monoamine oxidase (MAO)-B inhibitors are therapeutically effective for motor symptoms; however, their effects on NMS in PD are yet to be fully assessed. Here, we aimed to explore the antidepressant-like effects of propargyl MAO-B inhibitors, selegiline and rasagiline, in mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) as a PD model, and to elucidate the mechanisms underlying these effects.

Region-specific deletions of the glutamate transporter GLT1 differentially affect seizure activity and neurodegeneration in mice.

Glial glutamate transporter GLT1 plays a key role in the maintenance of extracellular glutamate homeostasis. Recent human genetic studies have suggested that de novo mutations in GLT1 (EAAT2) cause early-onset epilepsy with multiple seizure types. Consistent with these findings, global GLT1 null mice show lethal spontaneous seizures.

Therapeutic benefits of 9-amino acid peptide derived from prothymosin alpha against ischemic damages.

Prothymosin alpha (ProTα), a nuclear protein, plays multiple functions including cell survival. Most recently, we demonstrated that the active 30-amino acid peptide sequence/P30 (amino acids 49-78) in ProTα retains its substantial activity in neuroprotection in vitro and in vivo as well as in the inhibition of cerebral blood vessel damages by the ischemic stress in retina and brain. But, it has remained to identify the minimum peptide sequence in ProTα that retains neuroprotective activity.