A number of biochemical and proteomic studies have revealed a diverse and vast assortment of molecules that are present at the synapse. It is now important to untangle this large
array of proteins and determine how it assembles into a functioning unit. Here we focus HSP inhibitor clinical trial on recent reports describing how synaptic cell adhesion molecules interact with and organize the presynaptic and postsynaptic specializations of both excitatory and inhibitory central synapses. “
“Although the accumulation of the neurotoxic peptide β-amyloid (Aβ) in the central nervous system is a hallmark of Alzheimer’s disease, whether Aβ acts in astrocytes is unclear, and downstream functional consequences have yet to be defined. Here, we show that cytosolic Ca2+ dysregulation, induced by a neurotoxic fragment (Aβ25–35), caused apoptosis in a concentration-dependent manner, leading to cytoplasmic Ca2+ mobilization from extra- and intracellular sources, mainly from the endoplasmic reticulum (ER) via IP3 Crizotinib receptor activation. This mechanism was related to Aβ-mediated apoptosis by the intrinsic pathway because the expression of pro-apoptotic Bax was accompanied by its translocation in cells transfected with GFP-Bax. Aβ-mediated apoptosis was reduced by BAPTA-AM, a fast Ca2+ chelator, indicating that an increase in intracellular Ca2+ was involved in cell death.
Interestingly, the Bax translocation was dependent on Ca2+ mobilization from IP3 receptors because pre-incubation with xestospongin C, a selective IP3 receptor inhibitor, abolished G protein-coupled receptor kinase this response. Taken together, these results provide evidence that Aβ dysregulation of Ca2+ homeostasis induces ER depletion of Ca2+ stores and leads to apoptosis; this mechanism plays a significant role in Aβ apoptotic cell death and might be a new target for neurodegeneration
treatments. “
“Local field potentials (LFPs) recorded from deep brain stimulation electrodes implanted in the globus pallidus internus (GPi) of patients with hyperkinetic movement disorders (dystonia and Tourette’s syndrome) have shown desynchronized activity at 8–20 Hz and synchronized activity at 30–90 Hz during voluntary movements. However, the impact of the speed of the motor task on these frequency shifts is still unclear. In the current study, we recorded LFPs bilaterally from the GPi in seven patients with hyperkinetic movement disorders during normal/slow and fast horizontal line drawing movements as well as during rest. In comparison with rest, the low beta band showed a significant decrease in power during the motor tasks. Low beta power was more suppressed with increasing speed of the movement on the contralateral side. In contrast, a significant increase in power was induced by movements in the high beta and gamma bands on the contralateral side.