Memoquin – a novel multi-target therapeutic opportunity for Alzheimer’s disease

Structure of memoquin (Credit: PLoS ONE)Memoquin is a quinone-bearing polyamine compound that has been found to be effective against Alzheimer’s disease (AD) – a degenerative disorder affecting the brain and causing dementia especially in later life – due to its muti-target approach. Not only, it acts as an anti-AD compound but it can also work as anti-amyloid and anti-oxidant.

Mechanism of action:

Memoquin works as an acetylcholinesterase and β-secretase-1 inhibitor. It is found to be 10 times more potent than donepazil, most potent anti-acetylcholinesterase.

Memoquin is also able to inhibit in a concentration-dependent manner BACE-1, one of the two enzymes involved in the amyloidogenic cleavage of the amyloid precursor protein.

Benefits:

Memoquin is thought to be an effective therapeutic compound for the treatment of a number of neurodegenerative disorders. It has been found to be effective against AD due to its “multi-target-directed ligand” design strategy as AD is caused by a number of biological changes in the brain.

Researchers have found in a mouse model that 15 mg/kg of memoquin could help to treat cognitive impairment including spatial, episodic, aversive, short and long-term memory. Episodic memory refers to the memory that depends on the ability to remember in a determined temporal and spatial context. It is usually affected by normal aging and dementia. Spatial memory is a form of episodic memory having space-time dimensions.

Memoquin is able to inhibit the beta-amyloid peptide- (Aβ-) induced neurotoxicity mediated by oxidative stress. However, “the cellular mechanism through which MQ reverses Aβ-induced neurotoxicity and amnesia is not clear at present.”

It is also effective in decreasing plaque number and functioning. The compound also exhibits anti-aggregation properties.

Reference:

Capurro, V., Busquet, P., Lopes, J., Bertorelli, R., Tarozzo, G., Bolognesi, M., Piomelli, D., Reggiani, A., & Cavalli, A. (2013). Pharmacological Characterization of Memoquin, a Multi-Target Compound for the Treatment of Alzheimer’s Disease PLoS ONE, 8 (2) DOI: 10.1371/journal.pone.0056870

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