RPS23RG1 Is Required for Synaptic Integrity and Rescues Alzheimer’s Disease–Associated Cognitive Deficits

RAB39B Deficiency Impairs Learning and Memory Partially Through Compromising Autophagy

“…Synapse structures were assayed using a transmission electron microscope ( Ung et al, 2018 ; Zhao D. et al, 2019 ). More details are provided in Supplementary Materials and Methods .…”

microRNA-34a (miRNA-34a) Mediated Down-Regulation of the Post-synaptic Cytoskeletal Element SHANK3 in Sporadic Alzheimer's Disease (AD)

“…Because inter-neuronal signaling in the human central nervous system (CNS) is achieved through a complex network of presynaptic and postsynaptic elements essential in the conveyance of both electrical and neurochemical information, we have focused our investigations on the structural and functional integrity of key pre- and post-synaptic components in the superior temporal lobe neocortex (Brodmann A22), an anatomical region targeted by the AD process. One recently characterized core element essential for the efficient operation of this complex inter-neuronal signaling network is the relatively abundant ~185 kDa proline-rich cytoskeletal scaffolding and post-synaptic density (PSD) protein known as SHANK3 (SH3-and multiple ankyrin repeat domains 3; encoded at human chr 22q13.33) (8, 8–13). Interestingly, disruption in the abundance of the postsynaptic SHANK3 cytoskeletal anchoring protein has been associated with neurological disorders including autism spectrum disorder (ASD), bipolar disorder (BD), Phelan-McDermid syndrome (PMS; 22q13.3 deletion syndrome), intellectual disability, schizophrenia (SZ), and sporadic AD (9, 10, 14).…”

“…SHANK proteins are essential to post-synaptic structure and function in connecting, linking, networking and anchoring neurotransmitter receptors, ion channels, and other integral membrane proteins to the actin cytoskeleton and in the normal “homeostatic” operation of G-protein-coupled signaling pathways. Research evidence indicates that the massive SHANK3 protein (at ~185 kDa) forms an extensive post-synaptic cytoskeletal scaffolding network (involving the linkage of multiple SHANK3 proteins at the PSD) to which the smaller PSD-95 (at ~95kDa) protein is tethered usually via the SAPAP protein (~100 kDa); interestingly both SHANK3 and PSD-95 proteins, highly interactive components of the PSD complex, are reduced in abundance in the temporal lobe of AD-affected brain (13, 19, 20). SHANK3 post-synaptic scaffolding proteins thereby play essential roles in synapse formation and organization, synaptic cell adhesion, dendritic spine maturation and synaptic vesicle release (4, 11, 13, 21, 22).…”

“…Research evidence indicates that the massive SHANK3 protein (at ~185 kDa) forms an extensive post-synaptic cytoskeletal scaffolding network (involving the linkage of multiple SHANK3 proteins at the PSD) to which the smaller PSD-95 (at ~95kDa) protein is tethered usually via the SAPAP protein (~100 kDa); interestingly both SHANK3 and PSD-95 proteins, highly interactive components of the PSD complex, are reduced in abundance in the temporal lobe of AD-affected brain (13, 19, 20). SHANK3 post-synaptic scaffolding proteins thereby play essential roles in synapse formation and organization, synaptic cell adhesion, dendritic spine maturation and synaptic vesicle release (4, 11, 13, 21, 22). All SHANK species are abundantly expressed in the human CNS but exhibit different anatomical, developmental, and spatial patterns of expression; SHANK3 appears to have preferential expression in the human neocortex and hippocampus.…”

Overexpression of Human SNX27 Enhances Learning and Memory Through Modulating Synaptic Plasticity in Mice

“…The Morris water maze (MWM) was used to analyze reference spatial memory and was performed in a circular pool (diameter 120 cm) filled with water at 22 • C, using a modified protocol (Zhao et al, 2018). Around the pool, recognizable and contrasting shapes were provided as reference cues, and a transparent platform (diameter 10 cm) was submerged 1-2 cm under the water.…”