Molecule successful in treating Alzheimer's disease in mice

Researchers of the Universitat Autònoma de Barcelona (UAB), the Spanish National Research Council (CSIC) and the University of Barcelona (UB) successfully tested the ASS234 molecule in transgenic mice models of Alzheimer's diseases.

The ASS234 molecule inhibits the enzymes monoamine oxidase (A and B), acetylcholinesterase and butyrylcholinesterase, all involved in the biochemical processes causing neurodegenerative disorders, and displays a neuroprotective effect in transgenic mice models of Alzheimer's disease.

The patent of the molecule was recently granted by the United States to the Spanish company Inurrieta Consultoria Integral and is currently being presented to different pharmaceutical laboratories.

The ASS234 molecule was developed as a hybrid of two known molecules. One of them is donepezil, currently used to treat Alzheimer's disease. The other molecule is the PF9601N compound, an inhibitor of the monoamino oxidase B (MAO B) enzyme, patented and developed by researchers at UAB and CSIC, with proven neuroprotective effects in different experimental models of Parkinson's disease.

Researchers have worked for years on the design, synthesis and biological evaluation of new multipotent molecules capable of interacting with multiple cell targets affected by Alzheimer's disease. Among these, the ASS234 molecule stimulates cholinergic and monoaminergic transmissions, demonstrates an anti-apoptotic and antioxidant effect, and is capable of reducing the formation of amyloid-β oligomers, diminishing the number of amyloid plaques in transgenic mice. At the same time, the ASS234 molecule positively affects short-term memory recovery in mice with scopolamine lesions.

The research was conducted by Mercedes Unzeta, researcher of the Department of Biochemistry and Molecular Biology and of the Institute of Neurosciences (INc) at UAB; José Luis Marco Contelles, CSIC researcher at the Institute of General Organic Chemistry (IQOG); and F. Javier Luque, researcher of the Department of Physical Chemistry at the Faculty of Pharmacy and the Institute of Biomedicine of the UB (IBUB). The biochemical activity and pharmacological potential of the molecule was characterised by Irene Bolea (UAB) and synthesised by Abdelouahid Samadi (CSIC). Previous studies on the interactions of ASS234 with its possible targets were carried out by Jordi Juárez-Jiménez (UB).

Alzheimer's disease is a neurological disorder which greatly affects older people. It presents a complex neurodegenerative pathology which not only causes a progressive loss of cognitive abilities (memory, language, learning), but also produces psychiatric disorders (anxiety, depression, apathy, aggressiveness, etc.). Although the direct causes of the disease are yet unknown, the senile plaques, neurofibrillary tangle, oxidative damage to different cell structures and the low levels of acetylcholine neurotransmission are key factors in the development of this pathology.