This technology offers the potential for developing novel and effective treatments for mood- and memory-related disorders and neuropathic pain.
During learning, neurons produce an enzyme called protein kinase M zeta (PKMzeta) which is responsible for (1) maintaining newly strengthened connections between neurons, and (2) memory. PKMzeta is a truncation of PKCzeta that is expressed in neurons. It plays important roles in memory formation and storage. KIBRA (kidney and brain-expressed protein) has recently been shown to be associated with human memory performance. KIBRA has been linked both to normal cognitive performance and to Alzheimer's disease. Recent research suggests KIBRA functions in memory performance via interaction with PKMzeta. Numerous memory and mood disorders, and other disorders such as neuropathic pain, are believed to be due to pathological processes related to memory, including processes involving PKMzeta.
This technology is based on research involving two KIBRA-PKMzeta interaction inhibitors. One inhibitor, zetastat, acts by blocking the KIBRA-binding site in PKMzeta. A second inhibitor, K-ZAP, mimics and occludes the PKMzeta-binding site in KIBRA. Both inhibit the continual interaction between PKMzeta and KIBRA. Both inhibitors reverse established long-term potentiation (LTP) and disrupt established long-term memory. Therefore, the interaction between KIBRA and PKMzeta plays a significant role in the neurons' ability to maintain LTP and memory once it is formed. For example, compounds that inhibit PKMzeta activity after LTP formation leads to a reduction of LTP. Our research indicates the mechanism for blocking LTP and memory maintenance is through inhibiting KIBRA-PKMzeta interactions. This discovery offers the potential for developing novel and effective treatments for mood- and memory-related disorders and neuropathic pain.
• Potential for treating mood- and memory-related disorders and neuropathic pain.
• Can cross the blood-brain barrier.
• Can enter cell membranes to contact intracellular PKC zeta/PKM zeta within neurons.
The primary application for this technology is developing treatments for mood- and memory-related disorders and neuropathic pain.
Issued patent: US 11,446,264, “Memory manipulation via modification of protein kinase C zeta activity” (https://patents.justia.com/patent/11446264)
Pending patent: 18/941,696, “KIBRA-PKMzeta interactions in LTP and memory maintenance”
TRL 3 – Experimental proof of concept
This technology is available for licensing.
This technology would be of interest to facilities involved in research for developing pharmaceuticals that treat mood- and memory-related disorders and neuropathic pain. These include:
• Pharmaceutical companies engaged in drug discovery and development for CNS (central nervous system) disorders.
• Veterans Affairs (VA) and military medical research institutions focused on treating service-related neurological and psychological conditions.
• Military and defense research agencies studying the cognitive and psychological effects of combat, PTSD, traumatic brain injury (TBI), and performance enhancement in high-stress environments.
• Medical research laboratories, government and private research laboratories investigating novel treatments for neurodegenerative and psychiatric conditions.