Memory constraints and enhancers, a QR2 story

While most of our research thus far has focused on the dependence of long term memory on a complex array of mRNA and protein synthesis that occurs within relevant cells in the brain and key molecules involved in this process of memory consolidation, in a recent study, uniquely, we have identified a constraint on memory formation in the mammalian brain, namely the quinone reductase 2 enzyme (QR2).

We have found that QR2 acts as a constraint until it is removed by neuromodulators such as acetylcholine and dopamine, which are released in the brain by novel information. These neuromodulators are slowly lost during ageing, and are more acutely damaged in neurodegenerative diseases such as Alzheimer’s and Parkinson’s (AD and PD, respectively). The persistence of new memories and novel information are severely damaged as a result, and QR2 has also been found in elevated levels in post mortem brain samples of AD and PD patients. However, we have shown that removing QR2 from rodent models of dementia (both in aged animals and others that bear familial Alzheimer’s genes) corrects their memory and cognition (Rappaport et al. 2015). We have a patent on QR2 as a target for memory enhancement (US application number 15/126,291). Currently we aim to better understand signaling cascades upstream and downstream to QR2 and its function in different brain structures.

References

Rappaport AN, Jacob E, Sharma V, Inberg S, Elkobi A, Ounallah-Saad H, Pasmanik-Chor M, Edry E, Rosenblum K. 2015. Expression of quinone reductase-2 in the cortex is a muscarinic acetylcholine receptor-dependent memory consolidation constraint. J Neurosci 35: 15568-15581.

Muscarinic-Dependent miR-182 and QR2 Expression Regulation in the Anterior Insula Enables Novel Taste Learning (2020). Gould NL, Elkobi A, Edry E, Daume J, Rosenblum Kobi. eNeuro. 2020 Mar 20. pii: ENEURO.0067-20.2020. doi: 10.1523/ENEURO.0067-20.2020.

Dopamine-Dependent QR2 Pathway Activation in CA1 Interneurons Enhances Novel Memory Formation (2020). Gould NL, Sharma V, Hleihil M, Kolatt Chandran S, David O, Edry E, Rosenblum K. J Neurosci. 2020 Oct 12:JN-RM-1243-20.