CRMP2-binding compound, edonerpic maleate, accelerates motor function recovery from brain damage
Hiroki Abe1, Susumu Jitsuki1, Waki Nakajima1
1Yokohama City University Graduate School of Medicine, Department of Physiology, Yokohama, 236-0004, Japan.
Science (New York, N.Y.)
|April 7, 2018
Summary
Edonerpic maleate accelerates motor function recovery after brain damage by enhancing synaptic plasticity. This neural plasticity enhancer shows promise for improving rehabilitation outcomes in patients.
Area of Science:
- Neuroscience
- Pharmacology
- Neurological Rehabilitation
Background:
- Brain damage, like stroke, severely impacts quality of life.
- Effective medication-based rehabilitation strategies are lacking.
- Accelerating recovery from neurological injury is a critical unmet need.
Purpose of the Study:
- To investigate the therapeutic potential of edonerpic maleate for accelerating motor function recovery.
- To elucidate the mechanism of action of edonerpic maleate in promoting neural plasticity.
Main Methods:
- Administered edonerpic maleate to mice with motor cortex cryoinjury and nonhuman primates with internal capsule hemorrhage.
- Assessed motor function recovery and training-dependent rehabilitation.
- Investigated the role of collapsin-response-mediator-protein 2 (CRMP2) and α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic-acid (AMPA) receptor delivery.
Main Results:
- Edonerpic maleate significantly accelerated motor function recovery in mice through training-dependent cortical reorganization.
- The compound's efficacy was dependent on CRMP2, as it failed to improve recovery in CRMP2-deficient mice.
- Edonerpic maleate enhanced motor function recovery in nonhuman primates following internal capsule hemorrhage.
Conclusions:
- Edonerpic maleate acts as a neural plasticity enhancer by facilitating experience-driven synaptic AMPA receptor delivery.
- This compound demonstrates potential as a clinically effective agent for accelerating rehabilitation after brain damage.
- Targeting CRMP2 and neural plasticity offers a promising therapeutic avenue for neurological recovery.
Related Concept Videos
01:25Compounds Essential to Human Function
10.5K
The human body is composed of cells that are fundamentally made up of several different molecules. These molecules are essential to carry out all physiological processes in the body and are broadly classified into organic and inorganic based on their chemical structures.
Inorganic Compounds Essential to Human Functioning
Inorganic compounds essential to human functioning include water, salts, acids, and bases. These compounds are inorganic, i.e., they do not have a carbon-hydrogen bond. Water...
Inorganic Compounds Essential to Human Functioning
Inorganic compounds essential to human functioning include water, salts, acids, and bases. These compounds are inorganic, i.e., they do not have a carbon-hydrogen bond. Water...
10.5K
00:49Ligand Binding and Linkage
5.6K
Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked. In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence...
5.6K
03:02Organic Compounds
57.6K
All living things are formed mostly of carbon compounds called organic compounds. The category of organic compounds includes both natural and synthetic compounds that contain carbon. Although a single, precise definition has yet to be identified by the chemistry community, most agree that a defining trait of organic molecules is the presence of carbon as the principal element, bonded to hydrogen and other carbon atoms. However, some carbon-containing compounds such as carbonates, cyanides, and...
57.6K
01:17Accelerators
292
Accelerators in concrete serve as admixtures to speed up the hardening process, enabling the concrete to achieve early strength faster. Although accelerators do not necessarily impact the time it takes concrete to set, they reduce this time in practice. A common accelerator is calcium chloride, which is particularly useful for hastening early strength development in cold weather or for rapid repair jobs that require quick heat generation after mixing.
The effectiveness of calcium chloride can...
The effectiveness of calcium chloride can...
292
02:18The Equilibrium Binding Constant and Binding Strength
15.2K
The equilibrium binding constant (Kb) quantifies the strength of a protein-ligand interaction. Kb can be calculated as follows when the reaction is at equilibrium:
15.2K
02:54Coordination Compounds and Nomenclature
26.9K
In most main group element compounds, the valence electrons of the isolated atoms combine to form chemical bonds that satisfy the octet rule. For instance, the four valence electrons of carbon overlap with electrons from four hydrogen atoms to form CH4. The one valence electron leaves sodium and adds to the seven valence electrons of chlorine to form the ionic formula unit NaCl (Figure 1a). Transition metals do not normally bond in this fashion. They primarily form coordinate covalent bonds, a...
26.9K