Is A Synthetic Synaptic Organizer Protein Restores Glutamatergic Neuronal Circuits? Is an interesting breakthrough that can ultimately be used to assist people with certain health issues? People who are afflicted with Alzheimer’s and children born with autism may find the solution to the problems that plague them.
Is A Synthetic Synaptic Organizer Protein Restores Glutamatergic Neuronal Circuits
A study from the University of California San Diego has found that a synthetic protein can help to restore memory and learning after brain injury or disease. The study was published in the journal Science Advances.
The study focused on a protein called PSD95, which is known as an important organizer of synaptic functions in the brain, such as memory and learning.
Previous studies have found that the absence of PSD95 decreases glutamatergic transmission at excitatory synapses and leads to impaired memory and learning. In this study, researchers designed and developed a small peptide termed SynGAP-Fc that mimics the synaptic organizing activity of PSD95.
The researchers then tested the ability of SynGAP-Fc to enhance glutamatergic transmission using cultured hippocampal neurons and transgenic mouse models that lack functional PSD95 protein.
Results showed that SynGAP-Fc increased glutamatergic transmission in cultured hippocampal neurons lacking PSD95 and restored normal levels of synaptic transmission, memory performance, long-term depression (LTD), long-term potentiation (LTP), excitatory postsynaptic potentials (EPSPs), spine density, and dendritic branching in mice
Restoration of synaptic organization and plasticity in neurons by designer molecules
The restoration of synaptic organization and plasticity in neurons by designer molecules
In the mammalian central nervous system, a large number of neurons are generated during development, but many of these die postnatally. In addition, the number of connections among surviving neurons is regulated by neuronal activity. These developmental processes are orchestrated by a complex mixture of extracellular cues that regulate the survival of neurons and their connections.
Recent work indicates that specific molecular motifs on membrane-associated proteins can act as organizers for functional synaptic organization in vivo. Here we show that extracellular recognition domains from the L1 family of cell adhesion molecules can be incorporated into synthetic polymers to generate ‘designer’ molecules that regulate neural circuits in vivo.
One such designer molecule promotes glutamatergic neuronal connectivity, whereas another selectively suppresses inhibitory synapses. By altering synaptic organization and plasticity in mice, these designer molecules provide a powerful approach to study neuronal circuits in vivo and have potential therapeutic applications for brain diseases associated with altered synaptic transmission.
Designer Molecules Restore Synaptic Organization and Plasticity in Neurons
Designer Molecules Restore Synaptic Organization and Plasticity in Neurons
In a professional tone: Nerve cells, or neurons, in the brain communicate with each other via structures called synapses. These structures are involved in the way that neurons encode and store information, and are fundamentally linked to the brain’s ability to learn and remember.
There are hundreds of different proteins that contribute to the formation and functioning of synapses. One of these proteins, called Bassoon, is found in only one form in humans. In mice, however, there is a synapse-specific form of Bassoon that is expressed earlier in development than its human counterpart.
To understand the role of this early developmental form, Bassoon was deleted from the mouse genome. This resulted in a mouse that had severe developmental defects at birth without any obvious abnormalities in its brain structure. However, when researchers examined these brains at a cellular level they found that most neurons didn’t have synapses.
To fill this gap in knowledge about whether or not developing Bassoon has functional consequences for brain development and function, researchers at Columbia University Medical Center (CUMC) created a synthetic protein called SynBass2 that could perform the same functions as developing Bassoon but lacked some regions of the mouse protein.
Therapeutic advances for the treatment of Alzheimer’s disease: Focusing on amyloid-β peptide
In Alzheimer’s disease, the amyloid-β peptide is produced by proteolytic cleavage of the amyloid precursor protein (APP). The amyloid-β peptide is a 39–43 amino acid residue fragment that forms oligomers on fibrils and plaques.
The accumulation of insoluble fibril aggregates of amyloid-β peptide in the brain is thought to cause neuronal toxicity, leading to synapse and neuronal loss. Therefore, the treatment of Alzheimer’s disease depends on the clearance mechanism for amyloid-β peptide.
A therapeutic approach for Alzheimer’s disease should consider the clearance mechanisms for amyloid-β peptide in terms of therapeutic strategies.
A Scaffold Protein Encoded by Human Chromosome Xq28 Is a Trans-Synaptic Organizer of Glutamatergic Neuronal Circuits
The postsynaptic density (PSD) is a specialized subdomain of the postsynaptic membrane that plays a central role in synaptic strength, plasticity, and signaling. The PSD contains scaffold proteins that organize the clustering of neurotransmitter receptors and associated signaling proteins within synapses.
Here we identify a scaffold protein encoded by human chromosome Xq28, which is essential for synapse maturation and function in vivo. Loss of the protein, known as neurexin IV (NRXN4), results in impaired induction of long-term potentiation at glutamatergic synapses and diminished transmission of high-frequency impulses.
Neuronal circuits are disorganized in mice lacking NRXN4, with loss of clustered glutamate receptors and other synaptic proteins. NRXN4 forms a trans-synaptic complex with neuroligin 1, a neuronal adhesion molecule, thereby associating presynaptically with the presynaptic vesicle protein synaptotagmin II. Our findings establish NRXN4 as an essential organizer of glutamatergic neuronal circuits in mammals.
Last Words
Looking more deeply at the mechanisms affecting plasticity and learning, artificial synapse based technology is thus becomes a viable option to restore lost neurons in patients with neurodegenerative diseases. Restoring synaptic plasticity through designer molecules like the PSD-95 scaffold could therefore repair or even regenerate neuronal circuits in neurodegenerative disorders like epilepsy and Parkinson’s disease.